Index [application.wiley-vch.de] · 2017. 9. 27. · acute kidney injury (AKI) 1301 acute lung injury (ALI) 790, 796, 797 acute-phase proteins 1350 acute-phase reactants 1542 acute-phase

Index

aabatacept 1343Abl-family tyrosine kinase

inhibitor 1586absent in melanoma 2 (AIM2) 31

like receptor 997types 138

acetylcholine (ACh) 1486neuronal receptors 1499T lymphocytes 1487

acetylcholinesterase (AChE)inhibitors 1495

acetyltransferase 233acidosis 224, 894ACKR1/DARC expressed by

erythrocytes 635activated partial thromboplastin time

(aPTT) 834activated protein C (APC) 464, 739, 838activating transcription factor 3

(Atf3) 1448activation-induced cell death

(AICD) 1055activator protein 1 (AP-1) 231, 975,

1473acute inflammation 695

conditions, geneticsusceptibility 1331

inflammatory responses 1447acute kidney injury (AKI) 1301acute lung injury (ALI) 790, 796, 797acute-phase proteins 1350acute-phase reactants 1542acute-phase response (APR) 861, 1350

Acute Physiology and Chronic HealthEvaluation (APACHE-II) 847

acute rejectionantibody-mediated 1157caused by T lymphocytes 1157

acute respiratory distress syndrome(ARDS) 795

ADAMTS13 activity 837adaptive immunity 785, 876, 1147

antigen recognition by T cell 1005B-cell activation 1012central and peripheral tolerance

mechanisms 1004complement, role in 790immune cells, activators of 791immune responses 9, 273, 818, 947,

1092, 1147, 1316to allografts, immediate 1155inflammation triggered 1666

immune systems 1583immunoglobulins 1014other B-cell functions/B-cell

subsets 1015regulatory T cells (Tregs) 1010rheumatoid arthritis patients 1113

B-cell 1114T cells 1113

T cell subsets 1006T follicular helper cells 1010Th1/Th2 paradigm 1006Th17 cells 1009Th22 cells 1010Th9 cells 1010Th2 immunity 347

1691

Inflammation: From Molecular and Cellular Mechanisms to the Clinic, First Edition.Edited by Jean-Marc Cavaillon and Mervyn Singer. 2018 Wiley-VCH Verlag GmbH & Co. KGaA. Published 2018 by Wiley-VCH Verlag GmbH & Co. KGaA.

adaptive lymphocytes 342adaptive responses to transplants 1156adenosine A3 receptor 957adenosine diphosphate (ADP) 973

ribose moiety 87ribosylates Rho 87

adenosine triphosphate (ATP) 999,1283, 1313

ATPase 1306dependent sodium pumps 1302

binding cassette transporters 1280demand 1318dependent molecular

chaperones 817adenylate cyclase toxin CyaA 85adherens junctions 442

components 470adherent platelets 423adhesion molecules 1154, 1521

on colonic endothelial cells 461adipocytes 327, 1228adipokines 922, 1235adiponectin 924

dendritic cells 924lymphocytes 924macrophages 924neutrophils 924NK cells 924

adipose-derived stem cell 1205adipose inflammation

impact on local biology 1205obesity complications 1206

adipose tissue 1199, 1226, 1227inflammation, in obesity 1202

adipsia 861adjuvants

adjuvant system 3 (AS03) 147aluminum compounds 144combinations 157for human use 144induced peripheral

inflammation 655ADM. see adrenomedullin (ADM)ADP. see adenosine diphosphate

(ADP)adrenergic receptors (ARs) 1497β2-adrenergic receptors (β2ARs) 1500

adrenocorticotropic hormone(ACTH) 917, 1430, 1488,1489

adrenomedullin (ADM) 1549antibody 1595MR-proADM, elevated levels 1550

advanced glycation end product(AGE) 1239

AGE-RAGE axis 1239aeroallergen 185afferent neuronal signals 873afferent vagus 873age-related macular degeneration

(AMD) 1354aging 713, 1226

IL37-tg mice 506physiological process of 696

Aicardi-Goutieres syndrome 188AIM2. see absent in melanoma 2 (AIM2)airway epithelium, response to

allergens 998airway hyperresponsiveness 504Akt/protein kinase B (Akt/PKB)

1230, 1231, 1672aldehyde dehydrogenase 292aldolase 818aldosterone 917alkylthiyl radicals (R-S•) 706alkyne-containing jadomycin 1675allergen sensitization 1000allergen-specific IgE antibodies 996allergic asthma 292allergic disorders 375, 995allergic inflammation 374, 996, 997,

1004antigen recognition by T cell 1005B-cell activation and fate 1012central and peripheral tolerance

mechanisms 1004cytokines 1015–1017immunoglobulins 1012, 1014inflammatory response,

mechanism 996other B-cell functions and B-cell

subsets 1015regulatory T cells (Tregs) 1010T cell subsets 1006

1692 Index

T follicular helper cells 1010Th9 cells 1010Th17cells 1009Th22 cells 1010Th1/Th2 paradigm 1006

allergic rhinitis 347, 559allergic sensitization 798, 999allergy, classical 995alloantigens 1151allodynia 676alloimmunity 1054, 1150allosteric effects 633alpha-1-antitrypsin 749

anti-inflammatory properties 490alternatively activated macrophage

(AAM) 345alternative pathway (ACP) 1354alum 144aluminum phosphate 144aluminum salt combination (AS04)

adjuvant 145alveolar macrophages 185, 949Alzheimer’s disease 1489, 1502

patients with AChE inhibitors 1502American College of Rheumatology

(ACR) 555aminoalkyl glucosaminide 4-phosphate

(AGP) 154amino-hexoses 22aminotransferase-to-platelet ratio

index 676AMP-activated protein kinase

(AMPK) 1384amphibians 1517amphiregulin 345amplification pathway 787amyloid-β (Aβ) deposits 1258anabolic pathways 976anakinra (IL-1 receptor

anatagonist) 482anaphylatoxin 10, 786–791

C3a 63anastomosis 229Androctonus australis hector

venom 106androgens 919angioedema 803

angiogenesis 229, 457, 465, 1118LPA and S1P, role of 674

angiogenin (ANG) 4 441stimuli 467

angiotensin II 1233ankylosing spondylitis 1116anoikis 738anorexia 657, 861anthrax 8antiallergy treatment 662antiapoptotic

factors 529signals 592

anti-B and T lymphocyte attenuator(BTLA) 1596

antibiotherapy 265antibiotics 1584

treatment 1545antibodies (Abs) 1592

allergen-specific IgE 996anti-APC 464anti-HMGB1 60anti-HSP60 IgG-type 818anti-IFNγ 37anti-OX40 539C5 blocking 803complement, activation 801dependent cellular cytotoxicity 995,

1015mediated autoimmune diseases 367production 792

anti-CD25-mediated TREG

depletion 1398anticitrullinated peptide antibodies

(APCA) 1107anticytokine 482antifibrotic effects 1355antigen-presenting cell (APC) 84, 144,

659, 791, 792, 1112, 1151,1379

on inflammation 839antigens 439, 824

Ag-presenting molecules 154Ag-specific humoral immunity 156Ag-specific T-cell 155Ag uptake 147allergen-specific memory 996

Index 1693

antigens (Continued )B-cell selection, in germinal

centers 1391driven expansion 319expression of transplant 1148glucose-lipid 21independent activation

mediators 1152nonspecific inflammation 1147,

1148presentation

in context of MHC class I 1007in context of MHC class II 1008transplant 1150

self 818shuttling 792specific adaptive immune

responses 1147specific CD8+ T-cell (CTL)

responses 151specific self-tolerance 1094

anti-IL2Rα (Daclizumab) 352anti-inflammatory 795

activities 1001, 1668, 1670, 1673,1674

adipokine 1227cytokines 12, 229, 496, 499, 1163,

1363, 1429, 1488, 1524soluble cytokine receptors 1369soluble decoy toll-like

receptors 1371soluble ST2 1371soluble TREM-2 1372toll-like receptor-mediated

immune responses 1369drug 265, 1674growth factor 467master 1228mechanisms 1372

genes/proteins 1351mediators 1523monocyte subsets 1524properties 499, 601responses 1500stimuli 234

antimicrobialactivities 727

chemotherapy 1584itaconate 955peptide 175, 400, 441, 1092proteins 57

antineutrophil cytoplasmautoantibodies (ANCA) 260,264

antinuclear antibodies (ANA) 1073antioxidant

activity 870free radical scavengers 710harmful or beneficial 712response element 712supplementation 712

anti-programmed cell death ligand(PDL1) antibody 1596

anti-T-cell immunity 820antithrombin (AT) 837, 838

adaptive immune cells 1203levels 837macrophage infiltration 1201, 1203,

1212neutralizes coagulation enzymes 837

antithymocyte globulin 1163antivirulence factor therapies 1584anti venom 111

inflammation 110–111Myrmecia genus 111

anxiety 861APC. see antigen-presenting cell (APC)apocynin 1265apolipoprotein E (ApoE)

deficient mice 486null mice 665

apoptosis 299, 738, 917, 949, 959, 1314associated speck-like protein 138differentiation program 262inhibition 1321

apoptosis-associated speck-like proteincontaining CARD (ASC) 31

knockout 145apoptotic cells 228, 789, 1305, 1351A proliferation-inducing ligand

(APRIL) 1076BLyS receptors transmembrane

activator 1076arachidonic acid 869, 1449

1694 Index

metabolism 791pathway 1672

area postrema (AP) 1487, 1489arginase activity 956L-arginine 459aristaless-related homeobox (Arx) 442β-arrestin 635, 790arthritis 1447

ischemia-reperfusion experimentalmodels 60

arthritogenic alphaviruses 1354articular diseases 1105aryl hydrocarbon receptor nuclear

translocator (ARNT) 133asparagine endopeptidase (AEP) 735aspartic acid (D20)

in exon 1 503Aspergillus fumigatus 36, 181, 504,

1353, 1354Aspergillus versicolor 1587aspirin 1672asthma, allergic 292astrocytes 530, 776astroglia 1256, 1257AT. see antithrombin (AT)atherogenesis 1283atherosclerosis 457, 715, 818, 1199,

1229, 1279–1281macrophage inflammatory pathways

in 1291mediators of inflammation 1283

chemokines 1286cytokines 1283interferons 1285potential of dietary changes

1286targeting inflammation 1286

mouse models of 1280pharmacological intervention 1288

activating transcription factor 31292

anti-TNF therapy 1290CANTOS 1290CIRT 1290ENTRACTE clinical trial 1290JUPITER trial 1289statin therapy 1289

targeting IL-1β withCanakinumab 1290

atopic dermatitis 347, 643, 1099ATP. see adenosine triphosphate (ATP)Atractaspis engandensis 102AT1R/AT2R activation 1235ATX-LPA-LPA1,4,6 axis 674atypical chemokine receptors

(ACKR) 632, 635atypical hemolytic uremic syndrome

(aHUS) 1354autoantibodies 799, 818, 1316autoimmune 821, 1053, 1054, 1094,

1380, 1382, 1391diseases 329, 482, 785, 819, 918,

1055, 1066, 1074monocytes and

macrophages 1071disorders 799, 1677hemolytic anemia 995and inflammation 300, 1053injury 1256polyendocrinopathy candidiasis

ectodermal dystrophy 1057regulator 1057tissue injury 1053, 1068, 1073

B lymphocytes 1069immune complexes 1068lymphocytes 1069monocytes/macrophages 1070systemic autoimmune diseases 1073tertiary lymphoid organs

(TLO) 1071T lymphocytes 1069

autoimmune regulator (AIRE)protein 1057

autoinflammation 1053, 1054diseases 1365syndrome 482

autonomic homeostatic reflexes 1490autophagocytosis 817autophagosome 137, 817autophagy 137, 817, 1314

associated HLA-B27 misfolding 1120chaperone-mediated 817macroautophagy 817microautophagy 817

Index 1695

autophosphorylation 589autoreactive lymphocytes 1393autosomes 137avidity 1151AXD consensus sequence 504azoxymethane-dextran sodium sulfate

treatment 659

bBacillus anthracis 84, 193, 1587Bacillus subtilis 423bacterial

antigens 820DNA 156flagellum 28infection 1396, 1545lipoproteins 1588membrane and endosomal Toll-like

receptors 32mRNA 32proteases 734replication 187toxins

genetics and pathobiology ofinfections 81

pathogenicity bymicroorganisms 81

bacterial artificial chromosome(BAC) 1393

bacterial PAMPs. See pathogen-associated molecular patterns(PAMPs)

bacteriophage therapy 1584bacteriotropin 6Bacteroides fragilis 552BALB/c mice (BMDCs) 825, 1398,

1399B- and T lymphocyte attenuator

(BTLA) 1163barotrauma 795basic helix-loop-helix (bHLH) 442basophils 293, 634, 971, 1001B-cell 292, 315, 341, 342, 365, 533,

536, 550, 785, 792, 927, 1225,1226, 1229, 1230, 1233, 1236,1316, 1343

activating factor 536

checkpoint mechanisms 1064clonal deletion of 1056deletion 1064developmental stages 1013dysfunction 1232failure 1229, 1233growth factor 590, 1232immune-mediated targeting of 714maturation factor 536receptor 792, 1004, 1063, 1666tolerance 1059

B-cell-activating factor (BAFF)receptor 536transgenic mice 536

β-cell dysfunction 1232bees, inflammation induced by

venoms 110–111biglycan 66, 1588

deficient mice 66bioassays 1675biochemical signal transduction

pathways 424bioenergetics 929

dendritic cells 929lymphocytes 930macrophages 930neutrophils 930

biofilm 1584bioinformatics 1330bioluminescence resonance energy

transfer (BRET) 502biomarkers 1190

for inflammation 1541, 1542panels of combined of 1551

bleomycininduced lung fibrosis 667induced pulmonary fibrosis 663, 675

blocking tissue factor activity 835blood-borne cytokines signal 1489blood-brain barrier (BBB) 538, 771,

772, 862, 870, 1255, 1488blood circulation 3BLT1 deficiency 665BLT2 inflammation, and tissue

homeostasis, role in 665blunt leukocyte–endothelial cell

adhesion 463

1696 Index

body mass index (BMI) 1226body temperature 861bone marrow 1065

B-cell progenitors 506derived mast cell 276stromal cells 598

bonemorphogenetic protein (BMP) 1121Bordetella pertussis 84Bothrops snake 103

bitten victims 100Bothrops asper snake venom 101,

104Bothrops jararaca 102Bothrops moojeni venoms 102venom 100, 102, 103

induced inflammation 105induced leukocyte 102

BoTXC3 676Bowman’s space 1078bradykinin 803brain

cholinergic muscarinic acetylcholinereceptor (mAChR)-mediatedsignaling 1495, 1501

communication 1501controlled symptoms 861derived immunoregulatory

mechanisms 1491endothelial cells 872function 1494neurotransmitter systems,

dysfunctions 1495nitric oxide synthases 1673plasticity 1526processing of febrile signals in 874

Braun’s lipoprotein 27briakinumab 352, 407broad-spectrum antibiotics 795brodalumab 408, 555, 557bronchial hyperresponsiveness 375bronchoalveolar lavage (BAL) 675

fluid 795brown adipose tissue (BAT) 865, 922

cC3a/C5a receptors 797, 798

antibodies 803

biological roles 798complement factors 1316convertase 1320convertase formation 786dependent rapid production 873

E-cadherin 733cadherin-related family member 3

(CDHR3) 999Caenorhabditis elegans 814, 1492Ca++ influx 896calcitonin gene-related peptide

(CGRP) 110, 1493calcium 703

diffusion neutralizes 440mobilization 789phosphate 145

calmodulin 703calprotectin 64calreticulin 789Campylobacter jejuni 28cancer 1199, 1393

immune evasion 229immunosurveillance 1393

Candida albicans 36, 181, 376, 1330,1397, 1426

infection 1397yeast cells 508

candidiasis 186carbon monoxide 1319carboxypeptidase A3 278cardiopulmonary bypass 1317cardiotrophin 1 (CT-1) 575cardiotrophin-like cytokine factor 1

(CLCF1) 575cardiovascular disease (CVD) 1199,

1279, 1285, 1286, 1674cartilage proteoglycans 820caspases 82, 529

activating and recruitmentdomain 28

domains 32caspase-1 1364

activation 1519deficient mice 486, 491inflammasome 488

caspase-11 82toxins modulating 82

Index 1697

Castleman disease 578, 582catecholamines 1372, 1489, 1500cathelicidins 278, 446

LL-37 expression 446cathepsin 787

cathepsin G 732–734cathepsin L 735cathepsin S 735

Caucasians 662C4b binding protein (C4bBP) 786, 839C57BL/6-DEREG mice 1398C-C motif ligand 2 (CCL2) 1282CCP. see classical complement pathway

(CCP)CCR-7

axis 636expression 917

CD-related inflammation 551CD3-CD56+ cells 317CD4+ CD25+ FoxP3+ Tregs 1096CD4+ Foxp3+ Treg cells 1203CD4+ T cells 530, 633, 1151, 1368,

1372helper T cells 534naïve T cells 1381OX40-OX40L signaling in 536population 398

CD8 coreceptor, on cytotoxicT cells 1150

CD8 memory 1398T-cell pool 1396

CD8+ T-cell memory 152, 280, 323,530, 595, 1397

CD11c stain:CD11c+ myeloid dendriticcell accumulation 1093

CD14++CD16+ monocytes 1001CD14/CD14 receptors 1547CD14-dependent fashion 26CD14 expression 920CD18-ICAM-1 interactions 463CD18 immunoblockade 463CD25+Foxp3+ cells 1383CD25-targeted diphtheria toxin 1394CD25+Foxp3- thymocyte

precursors 1379CD28 expression 1380CD28 homodimer interface 1598

CD36 expression 1291CD40 antibody 660CD56bright NK cells 317CD62 ligand (CD62L) 1064CD64, neutrophil expression 1550,

1551CD64 values 1551CD80, to T-cell-expressed CD28 590CD94-NKG2A heterodimers 324CD103, in Balb/c mice 1398CD146, endothelial expression of 470cDNA cloning 487cecal ligation and puncture (CLP) 27, 60celecoxib 658cell

activation 651adhesion molecules 461, 715, 1549apoptosis 916contact-dependent

suppression 1060death 1313, 1314demise 1313forming BBB 871function 1313hypoxia 129immune response 587integrity 1284interaction 404mediated abnormal wound

healing 675necrosis 706penetrating peptides 1590proliferation 175respiration 131signaling pathways

in inflammation 1667schematic representation 1664

sources 484stress 814

markers of 813surface antigens 26surface markers, and signature

transcription factors 316cell-cell contact 733, 735cell-cell interactions 1111central nervous system (CNS) 1255,

1485

1698 Index

centruroides noxius 106cerebrospinal fluid (CSF) 1372C1 esterase inhibitor 802C3 exoenzyme of Clostridium

botulinum (C3bot) 87c-Fos mapping 657C3 glomerulonephritis 799C3 glomerulopathy 800chaperones 813, 816Charcot’s joints 1567ChAT. see choline acetyltransferase

(ChAT)chemoattractant 57, 257, 279, 619,

627protein 792receptor CRTH2 344

chemokines 60, 175, 223, 227, 256,366, 404, 554, 619, 626, 628,631, 732, 875, 962, 1233, 1256,1486, 1520, 1521

CCL1-CCR8 axis 641CCL20 functions 1096, 1097CC receptor (CCR)7 1386CCR6 expression 1097, 1388CCR9 ligand 636clusters 628CXCR2, on neutrophils 107dual function 628family 1520glycosaminoglycan

interactions 1524inflammatory 627, 628ligand (CCL) 3 and 4 1552monomer, ribbon diagrams 630motif ligand 2 (CCL2), matrix 1201organ development 636receptors 219, 629, 632, 633, 639,

640, 642, 1486activation, two-step model 633expression by T-cell subsets 629nomenclature systems 626schematic depiction 632

recognition site 1 633scavenger 635superfamily, clinical applications 642synthesis 1523

chemotaxis 7, 619, 1549

inhibitory protein ofstaphylococci 958

ChemR23, expressing cells 1453chikungunya virus 1354chimeric antigen receptor (CAR)

1399Chlamydia-infected cells 65Chlamydia pneumoniae 191, 958

HSP60 31chloride ion secretion 439cholesterol 1279, 1280

containing membranes 82crystals 1283

in vitro 1283hypercholesterolemia 1190, 1451transport 1280

choline acetyltransferase (ChAT) 1499expressing 1491

cholinergicanti-inflammatory 1491signals 1490

chondroitin sulfate 277chromatin

immunoprecipitation-sequencing 232

remodeling 1431structure, and function 974

chromoblastomycosis 195chromosome 1q23.2 locus 1351chronic granulomatous disease

(CGD) 1266chronic obstructive pulmonary disease

(COPD) 953, 1173accelerated aging and inflammation

in 1188associated with

chronic inflammation 1173indoor air pollution 1174

central role of alveolar macrophagesin 1178

defective resolution of inflammationand repair 1187

accelerated aging 1188airway fibrosis 1189proresolving lipid mediators 1187

eosinophilic inflammation in 1180future implications 1189

Index 1699

chronic obstructive pulmonary disease(COPD) (Continued )

inflammasome activation in 1184inflammatory cells 1175

dendritic cells 1182eosinophils 1180epithelial cells 1175lymphocytes 1181macrophages 1176neutrophils 1179

inflammatory mediators 1183chemokines 1185cytokines 1183inflammasome 1184lipid mediators 1183proteases 1185

lymphocytes in 1182mucus hypersecretion and

hyperplasia in 1177oxidative stress, as a major driving

mechanism 1185pathology of 1174systemic inflammation in 1187

chymases 733chymotrypsin 733ciliary neurotrophic factor

(CNTF) 575circulating

neutrophils 1201pyrogens 871

citrate metabolism 955Citrobacter rodentium 193, 1397citrulline 703, 956

specific B cells 1114c-Kit inhibitor 1118classical complement pathway

(CCP) 1354deposition 1355

claudin 4 666clonal deletion 1056, 1057Clostridium botulinum 86Clostridium difficile 88, 193, 1334

associated colitis 1593clumping factor A (ClfA) 423cmv-1 gene 322coagglutination system 787coagulant 739

coagulationabnormalities 847

treatment during severeinflammation 847

modifications 862proteases 841proteins 845

coagulopathy, associated 833colitis

associated colon cancer 659chronic, T-cell transfer model 460enhanced thrombogenic

response 465mice deficient in IL-1R8 502

collagen-induced arthritis (CIA) 556, 657colonic arterioles 460colony-stimulating factor-1

(CSF-1) 220colorectal cancer (CRC) 659Colubridae (sensu lato) 100commensal microbiota 292common helper ILCP (CHILP) 342common lymphoid progenitor

(CLP) 342compensatory anti-inflammatory

response syndrome(CARS) 1428

complementactivation 785, 786, 791, 795

anaphylatoxin receptors 789antibodies 801opsonin receptors 788

adaptive immunity and chronicinflammation 792

adaptive inflammatory response, rolein 791

cascade 870continued 792fragments of 794

C5a 869in human diseases, role of 799

vasculitis 799innate immunity and acute

inflammation 790innate inflammatory response,

role in 791intracellular, evidence 793

1700 Index

pathways 785, 786alternative 786classical 786lectin 786

products 787, 788receptors for 788

proteinsC3 732fragmentation of 787

receptors 788, 792, 793strategies to block 802system 785, 1238uncontrolled 792

complementary and alternativemedicine (CAM) 1661

complete Freund’s adjuvant (CFA) 146compstatin 802computational networks 1677computed tomography 1567confidence interval (CI) 848connective tissue growth factor

(CTGF) 676constitutive production of CCL27

(CTACK) 1092contact hypersensitivity (CHS) 283conventional dendritic cells (CD11b�

and CD11b+) 1143conventional imaging techniques 1567conventional myeloid dendritic cells

(cDC) 1112convertases 786Coombs test 995COPD. see chronic obstructive

pulmonary disease (COPD)coreceptor IL-1R3 499coreceptor neuropilin-1 467cortical thymic epithelial cells, self-

peptide/MHC complex 1065corticosteroids 1189

biosynthesis 1468pathways 1468

corticosterone 1430corticotropin releasing factor

(CRF) 655, 899receptor 899

corticotropin-releasing hormone(CRH) 1470, 1488

induced IL-2 receptor expression 918cortisone 1470Corynebacterium parvum 1426COX. see cyclooxygenase (COX)C-reactive protein (CRP) 10, 482, 768,

1349, 1351, 1352, 1354, 1542,1543

CRP gene 1351values 1543

Crohn’s colitis 461Crohn’s disease (CD) 65, 352, 374, 400,

403, 445, 457, 460, 493, 537,661, 1141, 1336, 1399, 1478

immunodeficiencies in phagocytes ascause 1143

missing heritability 1141patients 446

Cromolyn 283Crotalus atrox snake venom 104crown-like structure 1203CRP. see C-reactive protein (CRP)cryoglobulinemia 1069cryopyrin-associated periodic syndrome

(CAPS) 482cryopyrinopathies 193crypt base columnar (CBC) 438Cryptococcus neoformans 1397cryptopatches 344, 348crystallographic studies 1149crystal structures of GPCRs 643C-terminal pentraxin domain 1352CTLA-4-dependent regulation 1392C-type lectin receptors (CLRs) 144,

181–183, 225, 997, 1263, 1369dendritic cell-specific intercellular

adhesion molecule-3-grabbingnon-integrin(DC-SIGN) 181

mannose receptor 182signaling pathway 187surfactant protein-D 182

cutaneous anaphylaxis 666cutaneous lymphocyte antigen

(CLA) 376, 1091CLA+ recirculating T cells 1092

C-X-C motif (CXC) ligand 1chemokines 445

Index 1701

cyclic adenosine monophosphate(cAMP) 459, 789

intracellular levels, toxinsmodulating 84

signaling pathway 84, 660PKA-CREB/CRTC2 pathway 660

cyclic guanosine monophosphate(cGMP) 459

cyclooxygenase (COX) 228, 1451, 1672chemokines 630, 631CX3CL1-CX3CR1 axis 632CXCL12-CXCR4 interactions 636CXCL12 gradient 636CXCL8 secretion 603CXCL12/Stromal Cell Derived Factor

(SDF-1) 1520cyclooxygenase-2 (COX-2) 538,

868, 1588dependent manner 1457enzyme system 104expression, cytokine-induced 658PGE2 production 872

inhibitors 701, 874, 877pathway 106targeting, using NSAIDs 1267

cyclophilin ligand interactor 536cyclosporine A 1673, 1674

triggered cAMP signaling 85CysLT receptors 664

acute and chronic inflammation,role in 666

cystathionine β-synthase (CBS) 707cysteine 619, 707

signal transducing element 709cysteinyl leukotrienes (CsyLT) 185,

965cystic fibrosis (CF) 265cystic fibrosis transmembrane

conductance regulator(CFTR) 440

cytochrome C 131cytochrome P450 700

myeloperoxidase 916cytokines 11, 175, 227, 366, 395, 465,

469, 573, 587, 590, 593, 862,868, 869, 875, 915, 921, 963,1283, 1331, 1364, 1521

binding 573and chemokines related to Th17

cells 399chemotactic 103dual-function 506gene expression 261inflammatory 257, 1523interleukin-1 family

IL-1α dual-function 484IL-1 superfamily 479

interleukin-12 family of 149, 539,1368

like factor 576missense coding mutations 508production 365receptors 589, 1369

interactions 588signal 589

secretion 365storm 798synergizing 587synthesis inhibitory factor

(CSIF) 601type I 961type II 961

cytokine superfamilies 589common beta chain 592

granulocyte colony-stimulatingfactor (G-CSF) 594

IL-3 593IL-5 593

common gamma chain 589GM-CSF signals 594granulocyte colony-stimulating factor

(GCSF) 598interferons 599

type I IFNs 599type II IFNγ 600type III IFNλ-1/2/3 600

networks in cellular immunity 603orphan type I cytokines 596

IL-13 597IL-14 597IL-32 597IL-34 597macrophage colony-stimulating

factor 598

1702 Index

type 1 cytokine superfamily 589, 961type II superfamily 598, 961

cytomegalovirus (CMV) 34, 322cytoplasmic receptors, bacterial DNA

and RNA 33cytosine plus guanine (CpG)

oligonucleotide 61cytosolic free radicals 132cytotoxic

CD90.1-specific antibody 823lymphocytes 996necrotizing factor 88NK cells 318proteins 259soluble factors 1255T cells 144, 148, 534, 1062

antigen 4 1065response 235

dDaboia russelli snake venoms 104damage-associated molecular pattern

(DAMP) 20, 57, 105, 175,821, 922, 956, 997, 1152, 1153,1304, 1423, 1485, 1583, 1587,1588

adenosine triphosphate 63agents targeting host

responses 1589biglycan 66danger signal receptors 58eosinophil-derived neurotoxin 66heat shock protein 61heme 65heparan sulfate 66high-mobility group box 1 60histones 62hyaluronan 65immunology, definition of 57interleukin-1α/interleukin-33 64mitochondria 62to modulate immune responses to

transplants 1153molecule 1591necrosis vs. apoptosis 58peroxiredoxin 67RNA/DNA 62

S100A8/ S100A9 64uric acid crystals 63

DAMP. see damage-associatedmolecular pattern (DAMP)

danger-associated molecular pattern(DAMP) 137, 791, 1279,1369, 1541

Darwinian evolution principles 971DC. see dendritic cell (DC)death domain (DD) 179, 529, 533decay-accelerating activity (DAA) 787decay accelerating factor (DAF) 786decision-making processes 587deep vein thrombosis (DVT) 464defensins 1587degradation pathway, for LPA and

S1P 674dehydrocorticosterone 11demethylase 233dendritic cell (DC) 177, 179, 226, 289,

295, 322, 347, 401, 404, 530,628, 629, 636, 640, 793, 824,876, 971, 996, 999, 1061, 1092,1094, 1096, 1150–1152, 1351

activation, CTLA-4-dependentsuppression 1378

in allergic inflammation 292, 298for effector Th2 immune responses to

allergens 294immunoreceptor 185induce Th2 immunity, different

subtypes 293inflammatory 1096, 1151

FcϵR1+ DCs 298medullary 637necessary and sufficient for induction

of Th2 immunity 292subsets 290T-cell

interaction 1112polarization 291

denitrification 704dense deposit disease 799, 800dephosphorylation 674, 813depletion of regulatory T cell 1379DEREG model 1397DEREG mouse strain 1393

Index 1703

dermatitis 376Dermatophagoides pteronyssinus 375dermis 1091developmental endothelial locus

(Del) 1524developmental steps, of new imaging

agents 1579dexamethasone 222dextran sodium sulfate (DSS) 460,

484, 552, 663colitis 464, 494, 557

diabetes mellitus 714, 1199, 1229,1488

metabolic syndrome 505type 1 714, 1225type 2 1225, 1226, 1228,

1231–1233, 1672inflammation causing vascular

disease in 1234nonpharmacological management

of inflammation in 1240obesity associated inflammation

in 1236diacylglycerol (DAG) 1666diaminopimelate (DAP) 28diapedesis 6, 627dicarbonyl compounds 1239dietary antioxidants 710dietary polyphenols 711dietary thiols 708diet-induced obese (DIO) mice 1202digoxin 408dimerization 178diphenylene iodonium 1265diphtheria-tetanus-pertussis (DTP) 144diphtheria toxin receptor (DTR) 1378disease-modifying antirheumatic drug

(DMARD) 557disintegrin 631disseminated intravascular coagulation

(DIC) 425, 833DNA

binding protein 1592binding transcription factor

RBPj 445binding trimer 814damage 318

decondensation 732methylation 1189repair mechanisms 707sensing molecules 193–195

cross-talk between PRRs 195signaling components of DNA

sensing molecules 194vaccine encoding HER2/neu

adjuvanted 155DNAX accessory molecule-1

(DNAM-1) 318DNAX activation protein 12 kDa in size

(DAP-12) 1372, 1591docosapentaenoic acid (DPA) 1457dopamine receptor D2 767dopamine signals 1500dorsal motor nucleus (DMN) 1490

of the vagus 1487dorsomedial hypothalamus (DMH) 865double-stranded RNA (dsRNA) 178Drosophila melanogaster 30drug development

antivirulence factor therapy/quorum-sensing inhibitors 1586

defensins/antibacterialpeptides 1587

engineered liposomes to clearexotoxins 1586

new antibiotic combinations 1586PAMPs 1584tyrosine kinase inhibitors 1586

dupilumab 1098dysbiosis 441

eearly ILC progenitor (EILP) 342EC. see endothelial cell (EC)ectopic fat 1227ectromelia virus 317Eculizumab 803edema factor (EF) 84edema formation, PGI2-IP pathway

role 654edema toxin (ET) 84effector memory T cells (TEM) 639effector phase 790efferocytosis 6, 366

1704 Index

EGFR. see epithelial growth factorreceptor (EGFR)

eicosanoid oxidoreductase (EOR) 1453eicosanoid production 791eicosapentaenoic acid (EPA) 1451elastase 732, 733electron paramagnetic resonance

(EPR) 696electron spin resonance (ESR) 696electron transport chain (ETC)

129reactive oxygen species, formation

of 130electrostatic interactions 633emphysema 1188emulsions

IFA and CFA 146MF59 146

encode erythropoietin (EPO) 1321ENCODE project 1142endocannabinoids 875endocarditis 1567endocytosed bacteria 278endocytosis 635endogenous

adjuvants 143antinociceptive mechanisms 899antioxidants 711cytokine inhibitors 1523opioid receptor ligands 898protease inhibitors 730pyrogens 862, 875, 1425

β-D-endoglucuronidase heparanase 66endometriosis 230endopeptidases 727endoplasmic reticulum (ER) 88, 974,

1207, 1227endosomal/cytoplasmic receptors viral

DNA and RNA 34endosomes 635endothelial barrier function 1595endothelial cell (EC) 5, 257, 460,

1150adhesion glycoproteins 461adhesion molecules 461

transcription-dependentexpression 462

dysfunction 457, 458, 464endothelial cell NOS 703, 1672organ-specific responses 844proliferation 466

endothelial derived relaxing factor(EDRF) 702

endothelial differentiation gene 2(EDG2/LPA1) 668

endothelial dysfunction 1235, 1239endothelial-leukocyte adhesion

molecule 1(ELAM-1) 1474endothelial-mesenchymal transition

(EndMT) 1118endothelial nitric oxide synthase

(eNOS) 459, 703endothelial protein C receptor

(EPCR) 840endothelin 875

endothelin-1 276, 459, 1189endothelium-dependent 458

hyperpolarizing factor (EDHF) 459pathways 460

endotoxemia 62, 1233endotoxin 4, 20

biochemical characteristics 21cell activation 25chemical structures 22clinical settings 24detection 23historical background 20natural ligands 24

shock 61tolerance 21, 26, 234, 1432

signature 1428translocation 23

enterobacteriacae 22envenomation 109environmental conditions 861, 863enzyme acetyltransferase arrest-

defective-1 (ARD1) 134enzyme-substrate combinations 1675Eomesodermin (Eomes) 316

NKp46+ cell subset 316eosinophil 293, 322, 345, 347, 634,

971, 980, 1001, 1204cationic protein 1002derived neurotoxin 1002

Index 1705

eosinophilia 996, 997esophagitis 374inflammation 292

EP2/EP4-cAMP-PKA signaling 660EP3-expressing MnPO neurons 874epidermal cell-derived thymocyte-

activating factor (ETAF) 12epidermal growth factor (EGF) 230,

439, 734, 840epigallocatechin-3-gallate

(EGCG) 1671epigenetics 971

based inflammation treatment 984,985

dysregulationacute inflammation with 978chronic inflammation with 979

and immunometabolism 980, 981language 973memory 977poised enhancer-promoter

regions 975principles 972successful inflammation 974, 977unsuccessful inflammation 978, 979

epinephrine (EPI) 1488, 1489epithelial cells 437, 438, 998

activation 345archetypal epithelial barrier 438cell fate

absorptive lineage 438enteroendocrine cells 441goblet cells 439paneth cells 441secretory lineage 439

lining 437, 442membranes 443, 1593mucosal barrier protection 1592

epithelial growth factor receptor(EGFR) 1177

amphiregulin ligand 344genes 673

epithelial homeostasis 443inflammation-induced

alterations 445Notch signaling pathway 444Wnt signaling pathway 443

epithelium 442epitopes 818

mapping 820EP3 receptor genes 874E protein family 342EP3-selective agonist 662Epstein-Barr virus (EBV) 34, 194, 324,

595eritoran 796, 1320erythrocytes 255, 788erythrodermic psoriasis 1094erythro-myeloid progenitor

(EMP) 220erythropoiesis 224erythropoietin 1321esalamine (5-aminosalicylate) 465Escherichia coli 83, 191, 278, 423, 672,

732, 816, 839, 1143, 1353,1424

enterohemorrhagic Escherichia coli(EHEC) 706

Shiga-toxigenic E. coli (STEC) 89estrogen

decreased production ofneutrophil 919

increase bone marrow progenitorB cells 919

eukaryotic cellsactomyosin cytoskeleton 87proteases 728

eukaryotic translation initiation factor4E-binding protein(4E-BP) 1384

exocytosis 259, 277exogenous opioid (EO) 899exogenous pyrogen 862, 866, 868,

869exopeptidases 727exotoxins 278experimental autoimmune

encephalomyelitis(EAE) 186, 492, 660

experimental fever in rats, schematicillustration 867

expressed sequence tag (EST) 628extracellular matrix 1525

proteins 663

1706 Index

extracellular signal-regulated proteinkinase (ERK) 179, 1065, 1205

extracellular vesicles 1151

ffactor-inhibiting HIF (FIH) 134

hydroxylates asparagyl residues 134familial Hibernian fever (FHF) 265familial Mediterranean fever (FMF) 264FAS-associated death domain-containing

protein (FADD) 180, 529Fas receptor 533fatal autoimmunity 1378fat cells

anti-inflammatory cytokine 506fat distribution 1226

fatigue 861fatty acids 1232

nitrated fatty acids (NO2FA) 705omega-3 polyunsaturated 1452saturated 1233short-chain fatty acid (SCFA) 1004,

1380unsaturated 1287

febrigenic signals 871febrile response 861Fenton mechanism 713fever 861

beneficial or harmful 876clinical aspects 875defined 862experimentally induced 866inducing agent 862inflammation 3physiological and neuroanatomical

considerations 862of unknown origin 1567

fibrin degradation products(FDP) 425, 845

fibrin formation 836, 844fibrinogen 420, 836, 846, 1349fibrinolysis 1549fibrinolytic pathways, during

inflammation 837fibrinolytic proteases 739fibrin-rich inflammatory matrix

PTX3-dependent promotion 1356

fibroblast 675, 1526derived extracellular matrix

proteins 1528growth factor 467, 657like synoviocytes 1109transdifferentiate into

myofibroblasts 1527fibrocytes 5fibrogenic growth factors 1527fibronectin 1349fibrosarcoma, MCA-induced 1394fibrosis 675, 1189ficolins 786flagellin 28, 1588flavin adenine dinucleotide (FAD) 703flavin mononucleotide (FMN) 703flaviviridae, 5’-triphosphate ssRNA 34flightless I homolog (Fliih) 1431Fluarix influenza vaccine 156fluid resuscitation 795fluorescence optical imaging (FOI) 1580focal adhesion kinase (FAK) 468Foerster resonance energy transfer

(FRET) 502follicle-associated epithelium (FAE) 640

cells 640follicular dendritic cell (FDC) 792follicular Th (Tfh) cells 1069Fonsecaea pedrosoi 195fontolizumab 352food allergy 374, 377Food and Drug Administration

(FDA) 21, 1211, 1677Forkhead box family (Foxo)

proteins 1188phosphorylation 1383

FoxC2 transcription factor 468Foxp3 expression 1390

Foxp3-deficient mice 1387Foxp3-driven diphtheria toxin

receptor 1378Foxp3-driven TREG phenotype 1378Foxp3DTR knock-in mice 1393Foxp3DTR transgenic models 1379Foxp3 essential mechanisms 1379FOXP3 gene 1011Foxp3 genetic deficiency 1060

Index 1707

Foxp3+ TREGS 1378control of immunity to self-

tissues 1391Francisella tularensis 194free fatty acid (FFA) 1205, 1206free radicals 696

induced damage 696mediated injury 715production, mitochondrion, role

of 699Friend retrovirus (FV)

infection 1396functional

abnormalities 464capillaries 1235imaging, to monitor disease

activity 1578fungal infections 1397

C. albicans 1427Fusobacterium nucleatum 317

ggamma amino butyric acid

(GABA) 865, 1256GABAergic neurons 655

gamma/delta T-cell activation 492gammaglobulin, hypergammaglobuli

nemia 578gasotransmitters 702gastrointestinal

function 485surgery 1543tract 438, 439, 1672

GATA-binding protein 3(GATA-3) 342

deficient TREGS 1387transcription factor 395

GC. see glucocorticoid (GC)GDP-GTP exchange factor (GEF) 634gene expression 232

profile 439score 1553

gene loci associated with susceptibility torheumatoid arthritis 1340systemic lupus erythematosus 1339ulcerative colitis 1337

gene markers 916

gene profiling 136genetically modified organism

(GMO) 1675genetic engineering 1663genetic susceptibility

for acute inflammatoryconditions 1331

general considerations 1335meta-analysis 1334

to homogeneous studypopulations 1331

patients with same predisposingcondition 1333

patients with same underlyinginfection 1331

genetic variant rs1059703 of IRAK-1,X chromosome 1334

genome-wide association studies(GWAS) 661, 1067, 1142,1257, 1330

genomic, inflammatory activation 872genomic loci, with autoimmune

diseases 1067geranyl geranyl pyrophosphate

(GGPP) 1588GH. see growth hormone (GH)ghrelin 925glia-derived neurotrophic factor

(GDNF) 1258glimepiride 1212glomerular basement membrane

(GBM) 800glomerular filtration

barrier 1302, 1303of proteins 799rate 1302

glomerular injurycomplement-mediated 800

glomerular mesangial cells 802glomerular sclerosis 802glomerulonephritis 264, 995glomerulosclerosis 799glucocorticoid (GC) 11, 869, 917, 1472

adversely affect NK cell activity 918genomic effect of 1471glucocorticoid receptor 1470historical perspective 1467

1708 Index

induced leucine zipper 1430, 1473induced tumor necrosis factor

receptor 1385mechanism of action 1471, 1472nongenomic effect of 1473overview 1467pharmacokinetics 1470pharmacological effects 1474

adaptive immunity 1474immunomodulation 1474innate immunity 1474other effects 1475

proinflammatory cytokine productionsuppression 1489

receptor antagonist RU486 1430therapeutic use of 1475

adrenal insufficiency 1477allergy and asthma 1476infectious diseases 1477miscellaneous 1477preventing graft rejection 1477principles 1475renal diseases 1476rheumatic disorders 1476

upregulate Th2-inducedproduction 918

glucoseD-glucose 22metabolism 1320

glucose-6-phosphatedehydrogenase 917

glucose 1 transporter (GLUT1) 982glucotoxicity 1232glutamate 1493glutamatergic neurotransmission 767glutathione 711

peroxidase 1186glycans 36glycemia, hyperglycemia 714, 1232,

1233, 1239glycerophospholipid metabolic

pathway 674glycinergic synaptic transmission

655glycolipids 30glycolysis 956, 982

aerobic 1383

enzymes 1383metabolism 130

glycoproteins 182, 440, 462, 533, 536,788, 1353

glycoprotein A repetitionspredominant (GARP) 1015

glycoprotein-130 receptor 1546glycosphingolipid (GSL) 30O-glycosylated serine 440glycosylphospatidylinositol (GPI)

24, 35glycolipid 35linked protein 1549

glycyrrhizic acid 60goblet cells 439, 440

synthesize 439Goodpasture disease 995gouty inflammation, acute 263GPR. see G protein-coupled receptor

(GPR)G protein-coupled inwardly rectifying

K+ (GIRK) channels 896G protein-coupled receptor (GPR)

GPR120 deficiency 1288Gpr18 gene 1456P2Y2 receptor 957

G protein-coupled receptor kinases(GRKs) 635

G protein-coupled receptors(GPCRs) 619, 651, 874,1212, 1287, 1450

LGR5 438for prostaglandin D2 639

G-protein-dependent cAMP-proteinkinase A (PKA)-mediatedsignaling 1497

G proteins 633, 789antagonist 1368coupling 790inhibitors 579

graft-vs.-host disease (GvHD) 1378graft vs. host rejection 530granule-mediated cytotoxicity 315granulocyte macrophage colony-

stimulating factor(GM-CSF) 38, 109, 220,751, 1429

Index 1709

granulocyte-monocyte colony-stimulating factor(G-CSF) 150, 592, 594

granulocytes 1498granulomatosis 264granzyme B 787, 1552

mediated killing 1378GroES (HSP10) molecules 816growth factor-independent 1 342growth factor receptor-bound protein 2

(GRB2) 1065growth hormone (GH) 921

lymphocytes 922macrophages 921NK cell activity 922

GTPase-activating protein (GAP) 635GTPase RhoA-dependent cytoskeletal

derangements 1595GTPase signaling 1595guanine-nucleotide exchange factor

(GEF) 1666guanine triphosphate deoxynucleotide

(CpG) 31gut

associated lymphoid tissue(GLAT) 324

epithelial cells 996inflammation, chronic 460injury 59microbiome 1238

guttate psoriasis 1094

hHaber–Weiss reaction 713Haemophilus influenzae 957, 1179HapMap 3 project 1142hapten 2,4,6-

trinitrochlorobenzene 283haptotaxis 257Harpagophytus procambuns 1673health assessment questionnaire-disability

index (HAQ-DI) 555healthy obese phenotype 1227heart disease 499heat shock element (HSE) 814heat shock factor (HSF) 814

monomeric nature of 814

heat shock proteins (HSPs) 30, 61,813, 821, 824, 956

anti-inflammatory protective effectsof 820

biological function of 813chaperone functions of 816in chronic inflammatory

diseases 824coinducer 823endogenous upregulation 823families in mammals and typical

microbial homologues. 814HSP60 818

molecule 816, 820mycobacterial 818

HSP70chaperone 817peptide B29 823as prominent peptide donor for

MHCII ligandome 817protective effect of 820T-cell cross-reactivity 819

HSPH (HSP110) molecules 817HSP90 inhibitors 61immunology of 817as inflammatory mediators 821peptides 822, 824

dendritic cell (DC) 824prokaryotic, immunodominance

of 817self-HSP, cross-reactivity with 818specific CD4+ T cells 825

heat shock response 815molecular basis of 814triggers for 815

Helicobacter pylori 28, 178, 957infected gastric tumor 659

Heligmosomoides polygyrus 1391mouse infection model 1399

helminthimmunity 372infections 345

helper T cell 395, 1058hemagglutinins 317, 323, 1353hematological tumors 642hematopoiesis 1546hematopoietic stem cell (HSC) 593

1710 Index

heme oxygenase-1 65hemodynamic management 1301β-hemolysin 83hemolytic purpura 801hemolytic uremic syndrome

(HUS) 800, 801hemopexin 65hemophagocytic

lymphohistiocytosis 497Hemophilus influenzae 1353hemorrhagic shock 1317hemostasis 1212hemostatic systems 425hen egg white lysozyme (HEL) 1056heparan monomers 1588heparan sulfate 631heparin 277

chitosan complexes 282enhances DNA-I-dependent

chromatin degradation 1077induced thrombocytopenia 424

hepaticCD49a+ NK cells 319encephalopathy 1495iNKT cells 1492stellate cell 1206

hepatitis A virus (HAV) 144hepatitis B virus (HBV) 144, 324

vaccine 157hepatitis C virus (HCV) 33, 1069hepatocyte growth factor (HGF) 467,

1176activator 467

hepatocytes 1227herd immunity 143herpes simplex virus (HSV)

glycoproteins of 34Herpesviridae 322hexokinases 982HIF. see hypoxia-inducible factor (HIF)high-density lipoprotein (HDL)

cholesterol 1233high endothelial venule (HEV) 637,

677high-fat diet (HFD) 1201high flux electron transfer

pathways 699

high mobility group box-1(HMGB-1) 31, 821, 999,1062, 1153, 1518, 1591

high molecular weight B cell growthfactor (HMW-BCGF) 597

high-performance liquid chromatography(HPLC) 1675

high-throughput screening (HTS) 1676histamine 283, 375histocompatibility 60 (H60) family of

proteins 318histone 796, 842

acetylation 1431acetyltransferase (HAT) 1472deacetylases (HDACs) 823, 1472extracellular 1590H3K9 histone methyltransferase

G9a 1431H5N1 infection 1260H1N1 nucleoprotein antigen 148H7N9 strains 1354Hodgkin’s cells 533homeostasis 184, 344, 395, 538, 927,

972, 1142, 1520chemokines 627, 628, 1072molecular and cellular events 816protection 971

homodimers 180hormone-GR complex 1472horror autotoxicus 1377horseshoe crab (Limulus polyphemus)

hemolymph of 23host cell motility, toxins affecting 87host-environment interfaces 273host-pathogen

interactions 956systems 81

host proteasesfunctions, in inflammation 731

antigen presentation, andprocessing 735

antimicrobial functions 732coagulation 739complement system

activation 741fibrinolysis 739immunoglobulin cleavage 734

Index 1711

host proteases (Continued )inflammatory mediator

processing 732junction molecule

degradation 733matrix remodeling 736mucus 734receptor activation 736surfactant protein cleavage 734

identified in inflammation and 729and inhibitors, origin and

distribution 727inflammatory cells 728resident cells 728

mechanisms of action of 731house dust mite (HDM) 790HSF. see heat shock factor (HSF)HSPs. see heat shock proteins (HSPs)human adipose tissue 1228human alpha-defensin (HD)

HD-5 446HD-6 expression 446

human blood monocytes 503human CD161+ ILC1 subset 317human chemokines 620

receptors 623human chromosome 6 532human endothelial cells (HUVEC) 109human genome sequencing 816human herpesvirus 5 (HH5) 322human immunodeficiency virus

(HIV) 34, 324type 1 1549

human leukocyte antigens(HLA) 1148

locus 1055human maternal cells 1055human neutrophil elastase (HNE) 1185human papillomavirus (HPV) 144

vaccine 145human polymorphisms 191human rhinovirus (HRV) 999humoral immunity 639, 792, 1120hyaluronan 65, 11533-hydroxy-kynurenine 773hydrogen peroxide 700, 701hydrogen sulfide 706, 707, 1319

N-hydroxy-L-arginine 70318-hydroxyeicosapentaenoic acid

(18-HEPE) 1451hydroxyl ions 7013-hydroxy, 3-methyl glutaryl coenzyme A

(HMG-CoA) 158815-hydroxyprostaglandin dehydrogenase

(15-PGDH) 145311 β-hydroxysteroid

dehydrogenase 1470hymenoptera venoms 111hyperaggregability 464hyperalgesia 654, 676, 861hyperdynamic sepsis 1307hyperoxia 1317hyperresponsiveness 559hypersensitivity reactions

type II 995type III 995type IV 995, 996

hyperthermia 106hypomethylated CpG sequences 62hypoperfusion 1317hypothalamic-pituitary-adrenal

(HPA) 1486, 1487axis 654, 917, 1469

hypothermia 861, 877hypothyroidism 916hypoxia 129, 1227

acute vs. chronic hypoxia 136and antigen presentation 953causes of 130chemotaxis in 951include erythropoiesis 129and innate immune cell

survival 950molecular sensor signaling 131nuclear factor κB 135oxygen sensing 130phagocytosis in 952physiological response to 949pulmonary vasoconstriction 1319in regulating innate immune cell

function 949role in bacterial killing 952secretory function in 952tissue 263

1712 Index

hypoxia-inducible factor (HIF) 133,922, 1314

HIF-1α 981phosphorylation 134

HIF-1 acetylation 134HIF-1α/HIF-1β dimer 133target genes 134

iIBD. see inflammatory bowel disease (IBD)idiopathic pulmonary fibrosis

(IPF) 675IFN. see interferon (IFN)Ig. see immunoglobulin (Ig)ignorant conventional T cells

(Tconv) 298IkappaB kinase beta (IKK-β) 1230

deletion 490IL. see interleukin (IL)ILC. see innate lymphoid cell (ILC)imaging

modalities, comparison betweendifferent 1569

of myocardial inflammation, imagingof 1577

of systemic infections 1575imiquimod 155immune

activation 1549adherence clearance 788cell activation 790cell death, subversion of 958cell recognition, pathogen avoidance

of 957cell trafficking 788, 789

neural regulation 1496deficient nonobese diabetic mice 61inflammation

Th17 expansion, role of 661network, type I 328reconstitution inflammatory

syndrome 1596response 1031

to infection 322responsive gene 1 (Irg-1) 955stimulating complexes

(ISCOMs) 144, 148

system 818aberrant activation 1070defined 19

immune tolerance 1054APC-presenting autoantigen,

tolerogenic signals of 1061B-cell tolerance 1057bystander activation 1068central tolerance 1056costimulation activation 1068dead cell clearance defects 1068environmental factors 1067immune privilege sites 1062induced Tregs (iTregs) 1061infection/tissue injury 1067molecular mimicry

by adjuvants 1067by antigens 1067

natural Tregs (nTregs) 1061peripheral tolerance 1058regulatory T cells 1059self-antigen, modification of 1068T-cell anergy 1059T-cell tolerance 1056

immunization 818, 1265immunodeficiencies

mice 460in phagocytes 1143

immunodominantantigens 820proteins 820

immunodulatory cytokines 281immunodysregulation,

polyendocrinopathy,enteropathy, X-linked(IPEX) 1392

immunogenic nucleic acids 60immunoglobulin (Ig) 222, 225, 317,

457, 589, 734CAM family members PECAM-1/

CD31 469gene 1056immunoglobulin G (IgG) 422immunoglobulin A (IgA)

nephropathy 1069producing plasma cells 640

immunoglobulin E (IgE)

Index 1713

immunoglobulin (Ig) (Continued )antibodies 275dependent mast cell responses 366FcϵRI activation 279mediated hypersensitivity 995production 591, 996

immunoglobulin G (IgG)antibodies 786immune complexes 796

immunoglobulin M (IgM)antibodies 786

immunological disorders 861immunology, definition of 57immunometabolic

coupling 982imbalance 980

immunometabolismand acute inflammation 981and chronic inflammation 980

immunomodulation 1597, 820immunopathology 1394immunoproteasome 735immunoreactivity 818immunoreceptor tyrosine-based

activation motif (ITAM) 317immunoregulation 219, 223, 228immunostimulants 530

ligands 143, 157properties 57regimens 1596

immunosuppression 226, 229, 232,664

drug 677protocols 1147

immunotherapy 824Incomplete Freund’s adjuvant (IFA) 146

oil-in-water emulsions 147indocyanine green (ICG)–enhanced

fluorescence optical imaging(FOI) 1580

indoleamine-2,3-dioxygenase(IDO) 773, 1112

indomethacin-treated wild-typemice 655

induced Tregs (iTregs) 1061inducible T cell costimulator

(ICOS) 1386

ICOS-ICOSL interactions 348infection 8, 341

agents 795suspected systemic, and local

infections 1574inflammasome 192, 742, 792, 796,

1184, 1205, 1237, 1283activation 138

mitochondrial and cytoplasmicactivities 137

pathway 145toxins modulating 82

inflammation 1, 6, 8, 319, 322, 341,342, 457, 626, 785, 787, 874,915, 1147, 1199, 1210, 1226,1313, 1372, 1545, 1567, 1673

inflammatory bowel disease(IBD) 348, 373, 445, 457,533, 549, 659, 734, 818, 1116,1136, 1486, 1488, 1674

anti-TNF-α 558central angiogenic stimulus 466delivers

microvascular permeability 468immunoblockade experiments in

animal models 464lymphatic transport function 468patients 460

morbidity and mortality 463inflammatory disorders 437, 739, 785,

815C5a, C5aRs and C3aR, role in 795chronic, genetic predisposition

for 727, 792, 1336psoriasis vulgaris and psoriatic

arthritis 1338rheumatoid arthritis (RA) 1340systemic lupus erythematosus

(SLE) 1339models 666

HSP in 819inflammatory mediators 107, 654, 817,

959, 962cytokines and chemokines 961microvesicles 965oxidants 959

inflammatory signals, peripheral 874

1714 Index

inflammatory skin diseases 1092, 1098alopecia areata 1099atopic dermatitis 1098

influenza A 317inhibitor of DNA binding 2 (ID2)

expression 342inhibitory receptors 317innate immunity 175, 425, 479,

713, 785, 790, 876, 947,997, 1315

adaptive immunity, cross-talkbetween 1112

γ δ T cells 1113antigen presentation 958complement, role in 790damage-associated molecular

patterns activate 956function

impact of host-pathogeninteractions 956

microenvironmental factors inregulating 948

helper 2 cells 344IL-1 superfamily 479immune cells 785, 790, 996, 1203

activators of 791in acute inflammation 794

innate defense regulator 1591manipulating phagocytosis 958metabolic intermediates in

augmenting 955recruitment, preventing 957responses 102, 273, 956, 1147, 1148

inflammation triggered by 1664lipid mediators in 964

system activation 1315innate lymphoid cell (ILC) 315, 341,

591, 996, 997, 1002, 1094, 1111ILC2 and ILC3, therapeutic

harnessing of 351inositol triphosphate (IP3) 1666insulin 1230

hyperinsulinaemia 1229receptor 1230

signaling 1226, 1230substrate (IRS) 1205, 1207, 1230,

1231

resistance 1199, 1207, 1225, 1230,1231, 1233, 1239

adipocytes 1232insulin receptor substrate (IRS)

mRNA expression 1233proteins 1230, 1231

integrin (ITG) 1315activation 1518VLA4 627

intensive care unit (ICU) 1331intercellular adhesion molecule

(ICAM)-1) 1203interferon (IFN) 82, 1092

cytokines 178IFN-γ 341, 735, 916, 1425

prevented colitis induction 1388production 28receptor, IFNGR1 knockout 599,

600transcription factor 1097

interferon (IFN) α and β 1285, 1286IFNAR1 targeted deletion 600

receptor-dependent secondary geneexpression 1076

regulatory factor 179, 231, 232, 366,975

signature 188interleukin (IL) 834

IL-1 21, 1363family member 7 501functional role 508receptor antagonist 480, 658, 1523receptor family member ST2 498receptor type I 479, 482subfamily, of receptors 480superfamily 479–483

IL-1α 1518cell sources 484deficient mice 486dual-function cytokine 484endothelial cells 485as growth factor 485in healthy/disease cells 484historical background 483membrane 485, 486mouse cDNA cloning 483nuclear translocation 484

Index 1715

interleukin (IL) (Continued )precursor 484, 485systemic effects in humans 483

IL-1β 492, 654, 732, 862deficient mice 490, 491historical background 486immunoblockade 465LPS-induced synthesis 489NLRP3 inflammasome-dependent

processing 488noncaspase-1 processing 489precursor 489–491production by human

platelets 424production, regulation 487P2X7, inflammasome

activation 489regulatory regions 487systemic effects 487transcription/translation/

synthesis 487IL-1R

associated kinase 1430family 1365

IL-1R8 481deficient mice, primary

macrophages and DCs 502IL-1Ra anakinra, anti-inflammatory

potency 1365. See alsoanakinra

IL-1RI, deficient mice 495IL-2 149, 590, 1058

anti-inflammatory propertiesof 1366

derived from T cells 347IL-3

receptor α chain 593IL-4 395, 590

promote generation of Th2cells 365

secreted by Th2 cells 366IL-6 103, 573, 822, 1366, 1519,

1542, 1546biological activity and signaling

system of 573blockade therapy 579, 580blockade treatment strategy 580

clinical application of membersof 578, 579

dependent signaling 1366gene 1366IL6-receptor (IL-6R) 1257, 1285

complex associated withgp130 574

inhibitors, clinical application ofmembers 578

and its family of cytokines 573new members 575original members of 575and receptor components 575, 576receptor deletion 872receptor system, nonsignaling and

signaling receptorcomponents 574

redundant and nonredundantfunctions 578

soluble forms of nonsignaling andsignaling receptors 577

IL-7 591, 1203α chain 591receptor 317, 342

IL-8 89, 103IL-9 591

receptor α chain (CD129) 591signaling 345transgenic airway mouse model 375

IL-10 1366anti-inflammatory properties

of 1367subfamily receptors 600, 601

IL-11 575IL-12 492, 594, 1285

cytokine family 1367IL-12p40 deficiency 1285stimulate the generation of Th1

cells 365subfamily cytokines 594, 595

IL-15 150, 592essential for NK cell

homeostasis 327IL-17

blockers, therapeutic in CD 553clinical findings 556cytokine family 549, 557

1716 Index

cytokines, cell sources of 549, 552cytokines, in normal and inflamed

intestine, production androle 551

cytokines in psoriasis 553and its activity, secretion of 404neutralization, therapeutic efficacy

of 555in pathogenesis of autoimmune

diseases 492receptor 492, 550receptor A subunit 1098in rheumatoid arthritis 552, 556

IL-17Aglycoprotein 549in psoriatic arthritis 555

IL-17B, IL-17C, and IL-17Din immune-inflammatory diseases,

role of 557IL-18 492, 1284

binding protein 490, 493, 495blocking 493concept of 496coreceptor 1284deficiency 495, 1284genes 491in heart disease 494hemophagocytic syndromes 497human, natural neutralization 497IFNγ 492and inflammation 493precursor by caspase-1 491proinflammatory properties 493as protective cytokine 495receptor (IL-18R) 494, 1284signal transduction 491

IL-18 binding protein (BP) 494discovery 495gene 1365in immune responses 496regulation 496

IL-18Rdeficiency 1284

IL-18Rα 502chain 1364extracellular IgG-like

domains 481

IL-19 601IL-20 602IL-21 592

receptor-deficient animals 592IL-22 602

signals 602IL-23 595

and/or IL-1β stimulation 344receptor 550

IL-24 602IL-25

mediated promoting effects on Th2cell responses 558

production by commensalbacteria 558

production constitutive in humanand mouse liver 558

significantly ameliorates renalfunction and 558

IL-25R, expressing lamina propriadendritic cells 558

IL-26 603IL-27 595, 1367IL-33 499

binding 499discovery 498heterozygous mice

expressing 500in human disease 500nuclear function 499precursor 498, 499receptor 1389shares 499

IL-35 596, 1367producing regulatory T cells 1368

IL-36background 500receptor antagonist (IL-36Ra) 480role of 500

IL-37 502, 1364aging 506background 501binding studies 502crystallization 503disease models 504experimental colitis 505genes 491

Index 1717

interleukin (IL) (Continued )in human disease 507ischemic and damage models 505metabolic syndrome 505mRNA levels 506precursor 489, 507processing and release 503production 503protein 503, 508recombinant effects 504requirement for Smad3 507signaling complex 501spinal cord injury 505tg deficient, in IL-1R8 502tg mice 502, 505, 507translocation of 506

IL-37bfull-length precursor cDNA

of 504IL-38 508

dose-response suppression 508IL-1 family member 10, functional

role of 508ILCs

in adult tissues, maintenanceof 344

development, model for 343ILC2 (innate lymphoid cells)

activation 347in acute and chronic

inflammation 345and chronic inflammation 347deficiency 347expansion 345human, expresses 344in infection and chronic

inflammation 346and metabolic disorders 348and parasitic infection 345and viral infection 347

ILC3activated by IL-1β and

IL-23 344in acute and chronic

inflammation 348chronic inflammation, and

cancer 350

in clinic, targeting 351and commensal or pathogenic

bacteria 348during gut infection and

inflammation 349lineage 342vs. B/T development 342

International Association for the Studyof Pain (IASP) 891

intestinalepithelial cells 440immune system 640inflammation 447injury 1317lumen 447

intracellular adhesion molecule1(ICAM-1) 1474

expression 463intracellular nucleoside

triphosphate 63intracellular nucleotide oligomerization

domain (NOD)-likereceptors 1315

intracellular signal transduction 597intracranial aneurysm (IA) 658intraepithelial lymphocyte (IEL) 592,

641intraperitoneal thyroxine 916invariant natural killer T cells

(iNK T cells) 1524irritable bowel syndrome 1674ischemia-reperfusion 1152, 1155,

1313, 1317, 1318antioxidant therapy 1319clinical studies 1317injury 715, 803, 1313pathophysiology 1314phenomenon 1317therapeutic gases 1319therapeutic perspectives 1318tissue injuries 1316upregulate the MHC antigens

expression 1150ischemia tolerance, improving 1320ischemic conditioning 1318ischemic stroke 877isoforms Rho-A 88

1718 Index

itaconate 955Ixekizumab 408, 555, 557

jJanus kinase (JAK) 366

activation 1065enzymes 1671inhibitory peptide 1211JAK3 signal transduction

capability 590signal transducer and activator of

transcription (STAT)pathways 589, 592, 1671signal cascade 1430

junctional adhesion molecule(JAM) 257, 443, 469

kKaposi sarcoma-associated

herpesvirus 575Kc-derived PGE2 873kelch-like ECH-associated protein

(Keap1) 712keratinocytes 400, 554, 1092, 1094

activating mechanism 602trigger innate 1096

ketotifen 283kidney

injury 1078ischemia 1365normal, anatomy and

physiology 1302tubules and peritubular capillaries

inflammatory effects on 1304killer immunoglobulin-like receptors

(KIR) 183, 318molecules 319

killer lectin-like receptor subfamily Gmember 1-positive(KLRG1) 1386

kinin-kallikrein system 740Klebsiella pneumoniae 191, 732, 1353Krebs cycle 954, 955Kupffer cells 5, 224, 789, 870, 873,

1206, 1207kynurenine amino transferase

(KAT) 774

pathway, in schizophrenia 774kynurenine mono-oxygenase

(KMO) 774pathway in major depressive

disorders 774

llaboratory of genetics and physiology 2

(LGP2) 188lactoferrin 259lamina propria (LP) 1387Langerhans cells 154, 641, 949, 1096

in psoriasisimmunopathogenesis 1096

langerin 1092lateral parabrachial nucleus (LPB) 865LCE genes 1338Lebrikizumab (anti-IL-13) 352Legionella pneumophilia 191Leishmania infection 149

Leishmania donovani 182Leishmania lipophosphoglycan 36models 1398

leptin 867, 869, 923, 1200, 1207, 1233CRP interactions 1207deficiency 923lymphocytes 923macrophages 923neutrophils 923NK cell 923receptor 923

lesional IL-17-producing T cells 1094lethal bacterial infections 1424lethal factor (LF) 84leucine-rich protein 66leucine-rich repeat (LRR) 176leukemia inhibitory factor (LIF) 575leukocyte reprogramming 26, 1423, 1431

anti-inflammatory cytokines 1429clinical relevance 1427cross-tolerance 1425endotoxin tolerance 1423, 1426

affect anti-infectiousimmunity 1427

epigenetic 1431glucocorticoids 1430macrophage plasticity 1432

Index 1719

leukocyte reprogramming (Continued )microRNAs (miRNA) 1431regulatory signaling downstream

TLR 1430reversal 1429

leukocytes 102, 258, 425, 619, 626,1154, 1494, 1521

adhesion 263endogenous regulators of 462

endothelial cell adhesion 462extravasation, multistep model of 627HMGB1 promotes 60recruitment, during IBD 463reprogramming (See leukocyte

reprogramming)rolling (E-selectin) 462trafficking 1496

leukotaxine 8leukotrienes (LTs) 103, 277, 279, 374,

619, 965inflammation, role in 664leukotriene A4 (LTA4) 653leukotriene B4 (LTB4) 653, 923, 965,

1212, 1449hydrolase 1452receptor 664

leukoctiene C4 (LTC4) 653leukotriene D4 (LTD4) 352receptors 664, 669

Lewy body-like neuronalinclusions 1261

Lgr5-positive stem cells 439, 444daughter cells 438

ligand-protein interactions 1676ligand-receptor relationships 628, 629limulus amebocytes 419

limulus amebocyte lysate 23mammalian platelets,

comparison 420α2-3-linked N-glycolylneuraminic

acid 89lipid A releates to bacteria 22lipids

hyperlipidemia 1212, 1239lipid peroxyl radical (LOO•) 701lipid phosphate phosphatase

(LPP) 674

mediators 964, 1372, 1449biosynthesis, degradation, and

receptors of 652synthesis 1385

lipocalin-2 expression 1428lipopeptide adjuvanted vaccine

(LYMErixTM) 151lipopeptides adjuvant 151lipopolysaccharide (LPS) 19, 151,

177, 221, 422, 771, 862,916, 1257, 1351, 1424, 1426,1588

activated macrophages 955binding protein 1546fever model 870induced PD models 1260induced TNF 26in vitro capacity of 1425LPS binding protein (LBP) 24, 1333,

1426nonresponding strain 1425stimulation in human blood

monocytes 487tolerance 1331tolerized macrophages 1428

lipoproteins 177lipoprotein receptor-related protein

(LRP) 443liposomes 148

nano/microparticles 148lipoteichoic acid (LTA) 27, 1369lipotoxicity 1232, 1284lipoxins 228, 348, 1449, 1451

biosynthesis 1450lipoxin A4 (LXA4) 352, 965, 1449lipoxin B4 (LXA4) 965

lipoxygenase (LOX)enzymes 1449, 1451expression 12095-lipoxygenase 1454, 1672pathway 791

Listeria monocytogenes 82, 325, 706,1397, 1398

listeriolysin O (LLO) 82liver failure 837liver fibrosis 675liver injury 64, 1364

1720 Index

liver kinase B1 (LKB1) 1384deficient T cells 1385

LN. see lymph node (LN)locus coeruleus (LC) 1487, 1490low-density lipoprotein (LDL) 715,

1279cholesterol 1233LDL-LDL receptor complex 1468receptor (LDLR) 1280

low-grade inflammation, inhuman 1210

LOX. see lipoxygenase (LOX)Loxosceles spp.

envenomation 109venoms 108, 109

LPA. see lysophosphatidic acid (LPA)LPS. see lipopolysaccharide (LPS)LTs. see leukotrienes (LTs)lung dendritic cells

activated by epithelial cells 296lung injury 504, 1356lung lesions 795lupus nephritis 802, 1073

in kidney 1076aberrant tissue repair 1078chemokines recruit leukocytes 1077immune complex

glomerulonephitis 1076toll-like receptor activation 1077

morphology of 802Ly49 complex 318lymphangiogenesis 230, 457, 465lymphatic system 1154lymph endothelial cells 663lymph node (LN) 324, 344, 1072,

1112, 1151, 1154resident 289

lymphocytes 626, 918activating factor 11, 483activation gene 3 819, 1163with antigen 1058circulation

S1P/LPA, role of 676trafficking 425

lymphocytic choriomeningitis virus(LCMV) 1395

lymphoid lineage 593

α-lymphoid precursors 342lymphoid progenitor

cells 591and expression 341

lymphoid tissue inducer (LTi)cells 343, 344

lymphopoiesis 636lymphotoxin 365

alpha/beta (LTα/β) 344lysine 27

N-terminus 504lysolecithin. see lysophosphatidylcholine

(LPC)lysophosphatidic acid (LPA) 667

LPA6 674LPA-LPA1 signaling 675production

by ATX 672by phosphatidic acid-selective

phospholipase A1 (PA-PLA1α) 673

receptors for 668, 670S1P, pathophysiological roles 674structure 668synthetic, degrading, and action

of 672synthetic pathways and enzymes 671

lysophosphatidylcholine (LPC) 667,676

lysophosphatidylethanolamine(LPE) 667

lysophosphatidylglycerol (LPG) 667lysophosphatidylinositol (LPI) 667lysophospholipase D (lysoPLD) 671lysophospholipid 667lysosomal hydrolases 182lysosomes 635, 817

mMac1. see macrophages, antigen

complex 1macrophages 219, 224, 289, 327, 328,

347, 366, 401, 788, 916, 917,947, 949, 956, 1000, 1150,1151, 1227, 1228, 1233, 1283,1351, 1498, 1525

activation syndrome 497, 1598

Index 1721

macrophages (Continued )antigen complex 1 228, 1263

activation 803chemotactic protein-1 665, 1282colony-stimulating factor 594, 834dendritic cell precursor 219immunoregulatory properties 224infiltration 658inflammatory protein 8M1-type 1000in obese adipose tissue 1201phenotypes 222polarization 232tissue macrophage (TM) 228, 949

macrophages chemotactic protein-1(MCP-1) 658

macropinocytosis 789macrovascular disease 1234magnetic resonance imaging 1567,

1573major basic protein 1002major histocompatibility complex

(MHC) 590, 735, 1106, 1148,1596, 1666

class I, antigens 1149expression of 1150inhibitory receptors 317

class II antigens 822, 1149expression of 1150like “Y box 532

MHC-I-deficient environment 319MHC-I receptors 319molecules 1149, 1151

malaria 148, 426, 1398induced thrombocytopenia 426

mammalian nitrogen oxide cycle 704mammalian platelets 419mammalian target of rapamycin

(mTOR) 954, 1188, 1205pathway 1672

mammalian tissue mast cells 102manganese superoxide dismutase (Mn-

SOD) expression 715mannose-binding lectin (MBL) 786,

1155, 1349lectin 2 1333

mannose receptor (MR) 182

mannosyl fatty acids 185MAPK. see mitogen-activated protein

kinase (MAPK)maraviroc 642markers, of coagulation activation 848mass spectrometry (MS) 1675mast cells 273, 662, 788, 790, 1001,

1204, 1496activation (see mast cell activation)in adaptive immunity 279

antigen presentation 280DCs and effector T cells to sites

of infection, recruitmentof 280

dendritic cells and T cells todraining lymph nodes,recruitment of 280

as effectors of adaptiveimmunity 279

biology of 273degranulating (MCD) 111, 667, 995degranulating peptide (MCDP) 111enhancement of immunity by

boosting 281activators as novel vaccine

adjuvants 281synthetic granules 281

during immune responses, potentiallydetrimental roles 282

negative modulation of immunityby 283

overactivation 282in immune surveillance 275

activation by endogenous dangersignals 276

degranulation and secretoryresponses to pathogens 277

direct recognition ofpathogens 275

indirect recognition ofpathogens 276

strategic peripheral location 275in innate immunity 278

direct bactericidal activity 278induction of immune cell

trafficking to sites ofinfection 279

1722 Index

resistance to exo- andendotoxins 278

release prestored granules uponactivation 274

mastocytosis 375matrigel sponge 663matrix metalloproteinases

(MMP) 228, 469, 803, 1109MMP 3 555MMP-1 expression 666

matrix-synthetic myofibroblasts 1526MBL-associated serine proteases

(MASP) 786mechanistic target of rapamycin

complex (mTORC)mTORC2 complexes 1384

phosphorylation 1384mTORC1, T-cell biology 1381

medial preoptic area (MPO) 865median preoptic nucleus

(MnPO) 865medicinal herbs 1670medullary thymic epithelial cell

(mTEC) 1057, 1380melanocortin receptor (MSH) 927

MC1 and MC3 927melanocortins 927

lymphocytes 927macrophages 927neutrophils 927NK cells 927

melanocyte-stimulating hormone(MSH) 927

melanoma differentiation-associatedgene 5 188

melanoma differentiation-associatedprotein 5 35, 62

melatonin 711melittin 112membrane attack complex

(MAC) 787, 1316membrane-bound precursor

(tmTNFα) 530membrane cofactor protein

(MCP) 793membrane-type PGE synthase

(mPGES) 654

membranous glomerulonephritis(MGN) 799

idiopathic 800memory/effector T cells 289, 639memory inflation 323mepolizumab (anti-IL-5) 352meprin-β 734mercaptopyruvate sulfurtransferase

(MST) 707Merkel cells 1091mesangial cells 1305mesenchymal stem cell (MSC) 505,

1596mesenteric lymph nodes 348, 1017metabolic disorders 1674metabolic stress 322metabolism, and nutrient

availability 953metallo-beta-lactamase (MBL) 1587metalloproteinases (MMP) 264, 402,

530, 631, 733, 1201methacholine 375methionine 707

enkephalin peptides 348methotrexate therapy 556N-methyl-D aspartate (NMDA)

receptor 773methylene blue 870methylglyoxal (MGO) 1239methyl-4-phenyl- 1,2,3,6-

tetrahydropyridine(MPTP) 1262

MPP+ neurotoxicity 1264MF59 adjuvanted flu vaccine 147MHC. see major histocompatibility

complex (MHC)mice deficient

in caspase-1 490in NLRP6 494, 495

microarray technology 1676microbe/pathogen-associated

molecular patterns(MAMPs/PAMPs) 137

microbial invasion 1349microbial pathogens 175microbial pattern recognition

997

Index 1723

microbial proteases 753effects on

barrier function 744complement proteins 746cytokine/chemokine

production 746vascular permeability 745

and inflammation 742microbial recognition 1353microbial virulence factors 82microbicidal proteins 422microbiota

in allergic inflammation 1003induced gut inflammation 177

micrococcus prodigiosus 8microfold cells (M cells) 640microglia cells 530, 539, 1256, 1257

activation 776Mac1 receptor

and NADPH oxidase, couplingof 1264

microgliosis 1264microorganism/microbe associated

molecular pattern(MAMP) 19

microphages 6microRNAs (miRNAs) 234, 1142,

1371microsomal prostaglandin E synthase-1

(mPGES-1) 868microvascular dysfunction 1235, 1314microvascular endothelium 1154microvascular function 1239microvascularization 1315microvascular thrombus formation

in vascular beds 464migration inhibitory factor (MIF) 11,

1063, 1551milk fat globulin (MFG) 225misshapen-Nck interacting kinase-

related kinase (MINK) 1065mitochondria-derived peptides 957mitochondrial-associated membrane

(MAM) 188mitochondrial DNA (mtDNA) 58, 62,

1384mitochondrial dysfunction 1317

mitochondrial enzyme complexcytochrome c oxidase 129

mitochondrial growth stimulantactivity 1596

mitochondrial oxygencontrolled reduction to water 700sensing, cytochrome oxidase 131

mitochondrial respiratory chain 699mitochondrial ROS (mROS) 960mitochondrial superoxide dismutase

(mtSOD) 132mitochondrial transition pore

(mPTP) 1314mitogen-activated protein (MAP) 635,

789mitogen-activated protein kinase

(MAPK) 134, 152, 550signaling pathways 86, 1667, 1671signaling, toxins modulating 85

synergy between ET/LT 86modified vaccinia virus Ankara

(MVA) 1396molecular mechanism 219molecular trafficking 699monoclonal antibody 1098

SAP antibody 1355monocyte chemotactic protein

(MCP) 1228MCP-1 89, 109, 1203

monocytes/macrophage 219, 233, 401,530, 626, 628, 631, 949, 999,1000

activation and polarization 221CD14+ cells 1200functions 222–230

antigen presentation 226cytokine production and

inflammation 223immunoregulation 228migration 227phagocytosis 224vascular functions 229

molecular pathways and mechanismsregulating response 230–235

epigenetic regulation 232micro-RNAs 234signaling pathways 230

1724 Index

nonclassical 632origin and differentiation 219recruitment 956

monogenic autoimmunediseases 1066

Mono-Mac-6 cells 1429mononuclear cells 657

specific chemokines 1522monophosphoryl lipid A (MPLA) 21,

144, 145, 153monosodium urate (MSU)

crystals 63mouse chemokines 620mouse cytomegalovirus (MCMV) 319

infection, acute 323mouse mast cell protease 6

(mMCP6) 279mouse MHV coronavirus

infection 1395mouse T-cell line 483mRNA transcription 599MUC2 gene 446mucin (MUC) 734

domains 440granules, exocytosis 440proteins 439

Muckle-Wells syndrome 482mucosa-associated lymphoid tissue

(MALT) 1061mucosal-associated invariant T

(MAIT) 1070mucosal immunity 344, 636

CCR6+ and NCR+ ILC3 344and chemokines 640

mucosal ischemia 1592multicomponent receptor systems 573multidrug-resistant (MDR) 1584multidrug-resistant protein 1

(MRP1) 653multiple cellular functions 1673multiple sclerosis (MS) 659, 661, 793,

819, 1264, 1392, 1671, 1674multiplexed molecular markers 1552multiplicity of infection (MOI) 959multitarget drug discovery 1662muramyl dipeptide (MDP) 191, 1427muramyl tripeptide (MTP) 1427

murine alveolar macrophages 1429murine chromosome 17 532murine endosomal TLR7 32murine Ptx3 genes 1351musculoskeletal disorders 1567mycobacterial antigens 820mycobacterial lipomannan 25Mycobacterium avium subspecies

paratuberculosis 1143Mycobacterium bovis BCG

infection 1397Mycobacterium leprae 1397Mycobacterium tuberculosis 181,

325, 492, 503, 706, 819,958, 1586

HSP71 31Mycoplasma fermentans 27MyD88. see myeloid differentiation

primary response-88 (MyD88)myeloid cells 193, 329, 593, 788,

1367degranulation in 788dendritic cells 1096expressing 6-sulfo-LacNAc 1096

myeloid-derived suppressor cell(MDSC) 1163

myeloid differentiation primaryresponse-88 (MyD88) 1364,1430

adapter molecule 1430associated pathway 59binding 501dependent pathway 1426dependent receptor 83dependent signaling 179, 1371

by IL-1R8 for TLR signaling 501dimerization 1590homodimeric formation 1590in inflammation 105knockout mice 105protein 1590

myeloid inhibitory C-type lectin(MICL) 185

myeloperoxidase (MPO) 705, 1201myocardial infarction (MI) 715, 793,

1313myofibroblasts 675

Index 1725

myosin light chain kinase(MLCK) 459

Myrmecia genus ant venom 111

nN-acetylcysteine 1320N-acetyl-glucosamine (N-AcGlc) 27,

28N-deacetylase-N-sulfotransferase 1

(Ndst1) 1286N-acetylmuramic acid (N-AcMur) 28N-acetylmuramyl-L-alanyl-D-

isoglutamine 28N-acetyl-p-benzoquinoneimine

(NAPQI) 712α7nAChR agonists 1503NADPH oxidase (NOX) 696, 700, 916,

917, 1186, 1264, 1265activations 1265, 1314enzyme isoforms 700therapeutic targeting 1265

NAD+-sensing protein with lysinedeacetylase activity 983

nanotransducing regulatoryelements 709

nasal-associated lymphoid tissue(NALT) 281

natural antibodies 818natural cellular process 714natural cytotoxicity receptors 317

NKp46 (in mice and man) andNKp44 (in man) 344

natural killer (NK) 30, 183, 227,315–319, 322–324, 341, 400,492, 530, 534, 550, 592, 916,971, 1003, 1111, 1315

activation 318, 322, 920activating and inhibitory signals

regulate 321in men 919

CD27+CD11b- 320education/licensing 318gene complex-associated

CLRs 183–187activation receptors 183CLR signaling 186inhibitory receptors 185

and group 1 ILCs, in inflammation/infection 322

cells and other viralinfections 324

effector functions of 320evidence for distinct subsets

of 319Influenza virus 323Listeria monocytogenes 325memory 326mouse cytomegalovirus 322mycobacteria 325as partners in type 1 network 327Salmonella typhi 324

of human 316maturation 319receptor CD161 344T cell 600, 1003, 1070transcript 4 597

natural LPS ligands 25natural products 1661–1663, 1674

derived bioactive compounds 1668use of nanotechnology 1677

navamepent 1453necrotic cells 224, 1155, 1517Neisseria meningitidis 916, 1353neoplastic growth 861neovascularization 1118net filtration pressure (NFP) 1302neural pathways 874neural transmission 874neuraminidase 323neurodegeneration 1255–1257, 1264,

1265disease-modifying therapy 1265inflammation-related models

of 1259novel anti-inflammatory therapy

for 1265progressive, inflammatory

mechanisms of 1262neuroendocrine 915neurohumoral immunomodulatory

pathway 1489neuroimmune

communicatome 1486–1488bioelectronic medicine 1503

1726 Index

brain function in peripheralinflammation 1494

immune cells 1499trafficking, neural regulation

of 1496inflammation, neural sensing

of 1493inflammation resolution, neural

regulation of 1498nervous system 1492, 1496neurogenic inflammation 1493neurotransmitters, in neuronal

circuits controllinginflammation 1497

peripheral inflammation focusing oncholinergicmechanisms 1501

pharmacological anti-inflammatoryapproaches 1503

points of interaction 1492translational exploration 1502

neuroinflammation 1255–1257, 1488,1493, 1496

beneficial effects of 1258detrimental effects of 1258dysregulated 1262modulation of 1265reflex 1372

neuronal apoptosis inhibitory protein(NAIP) 28

neuronal nitric oxide synthase(nNOS) 703

neuronal thermoregulatorycircuitries 864

neurons 866, 1257derived self-compounds and

microglial Mac1 bridgesmicrogliosis and chronicneurodegeneration,interactions 1263

injured, form a self-perpetuatingvicious cycle drivingneurodegenerationprogression 1262

median preoptic nucleus(MnPO) 866

neuropathic pain 676

neuropeptide Y 927, 928, 1493neurotensin 278neurotransmitters 130, 862neurotrophic factors 1256neutralizing antibodies 145, 795, 1098neutrophil elastase (NE) 265, 734

elastase 2 1552neutrophil extracellular trap

(NET) 85, 103, 175, 423,425, 732, 796, 842, 843, 1111,1427, 1522, 1590

neutrophil gelatinase-associatedlipocalin (NGAL) 1524

neutrophils 104, 261, 278, 279, 325,327, 328, 401, 425, 536, 626,628, 732, 788, 790, 876, 915,916, 947, 949, 956, 966, 980,1097, 1154, 1315, 1524,1543

adhesion/migration 255–258to endothelial wall 256traffic 255transendothelial 257

apoptosis 261characteristics 253cytokine synthesis 260–261

IL1 and IL-1 receptorantagonist 260

IL-8 as model of chemokines 261modulation of cytokine expression,

and production byneutrophils 261

TNF-α 260derived catepsins 634functions 962glucocorticoids (GCs) increased

blood level 918hematopoiesis 254in pathology 262–265

autoimmunity against neutrophilcomponents 264

bacterial infection 263crystal-induced inflammation 263cystic fibrosis, neutrophil-mediated

tissue damage 265cytokine-induced inflammation,

rheumatoid arthritis 263

Index 1727

neutrophils (Continued )genetic disorders regulations,

hereditary periodic feversyndromes 264

tissue injury-inducedinflammation, ischemia-reperfusion injury 263

phagocytosis anddegranulation 258–260

degranulation 259phagocytosis 258

sequestration 263sources of oxidants in 960transepithelial migration 258

New Delhi metallo-beta lactamase(NDM-10) 1587

next-generation sequencing(NXS) 1330

NF. see nuclear factor (NF)NFκB RelB-dependent silent

heterochromatinformation 983

NF-κB. see nuclear factor kappa B(NF-κB)

nicotinamide adeninedinucleotide 700

Nippostrongylus brasiliensis 345, 558nitric oxide (NO) 37, 459, 462, 463,

697, 702, 923, 1230, 1428, 1672deficiency 460enzymatic and nonenzymatic

production 703H2S cross-talk 708indirect anti-inflammatory

effects 706interferon gamma (IFN-γ)-induced

production 706mRNA expression 845reactive intermediate (RNI)

peroxynitrites 104synthases (NOS) 697, 822, 868,

1314, 1544, 1672cNOS, defined 703

inducible nitric oxide synthase(iNOS) 703, 705, 917, 959,1203, 1432, 1672, 1673

nitrogen dioxide (•NO2) 697, 704

nitrotyrosine (NO2Tyr) 705NK. see natural killer (NK)NKG2D ligands 318NKp46 activation 317, 323NLR. see NOD-like receptor (NLR)nociception 112, 891, 893NOD-like receptor (NLR) 28, 137,

144, 188–193, 225, 441, 997,1423, 1488, 1518

classification and signalingpathway 190

family pyrin domain containing 3(NLRP3) 58, 1237

NLRC4 missence mutationThr337Ser 483

NLRP3 inflammasome 63, 66, 83,788, 798, 1237, 1239, 1283, 1284

activation by dopamine 1501NLRP3 knockout cells 138NLR proteins (NLRPs) 138, 192NOD1 and NOD2 191

signaling 192pyrin-domain containing 3 33

nonalcoholic fatty liver disease 1199noncanonical inflammasome

pathway 82noncanonical NFκB signaling 660nonclassical MHC-I molecules 318non-ELR CXC chemokines 631non-Hodgkin lymphoma 637nonlymphoid tissue-resident TREGS

1389non-MHC-I-based self-receptors 319non-NK hematopoietic cell types 315nonpermissive promoters 233nonshivering thermogenesis (NST) 863nonsteroidal anti-inflammatory drug

(NSAID) 654, 877, 1257nonthyroidal illness (NIST)

syndrome 916norepinephrine (NA) 862

preoptic area, role of 874norepinephrine (NE) 1488, 1489normal skin

immune organ 1091inflammation by polarized T-helper

cell subsets 1092

1728 Index

Notch intracellular domain (NCID)445

Notch signaling 444Notch transcription factor RBPj 445novel antibacterial agents 1586novel sulfido lipid mediator

conjugates, in tissueregeneration 1457

NOX. see NADPH oxidase (NOX)noxious stimulus 1517nuclear erythroid 2-related factor

(Nrf2) 712nuclear factor (NF) 550, 1366

activated T cells (NFAT) 1162interleukin-3 (NFIL3) 342kappa B 868

cascade 1519pathway 223, 446, 836

kappa-light-chain-enhancer 1667nuclear factor kappa B (NF-κB)

activation 58, 462, 466, 920inducing kinase (NIK) 192signaling 957, 1285translocation 1590

nuclear imaging 1567nuclear magnetic resonance

(NMR) 1675spectroscopy 1553

nuclear medicine techniques 1574nucleosome remodeling 232nucleotide-binding domain and leucine-

rich repeat pyrin containingprotein-3 (NLRP3)inflammasome 491

nucleotide-binding oligomerizationdomain (NOD) 59, 189

containing protein 1 (NOD1) 1427NOD2 risk haplotypes 1143receptors (See NOD-like receptor

(NLR))nucleotide pyrophosphate

phosphodiesterase(NPP) 672

nucleus tractus solitarius (NTS) 873,1487, 1489, 1490

nuocytes 344nutraceuticals 1212, 1670

oobesity 499, 505, 1199, 1213, 1226, 1488

associated inflammation in type 2diabetes 1236

associated low-gradeinflammation 1226

associated type 2 diabetes 1229induces inflammation in diverse

organs 1206phenotypes, and therapeutics 1210as profibrotic disease 1208

obstructive sleep apnea (OSA) 136occludins 733oil-in-water emulsions 144, 147oligomerization 188oligonucleotide (ODN) 156Omics technologies 1552oncogenesis 1546oncostatin M (OSM) 575open canalicular system (OCS) 419opioids 875, 901

peptides 899receptors

plasticity, and signalingpathways 896

and signaling 896opsonins 225, 786, 787, 789–791, 1543

antibodies 1584receptors 225, 789, 791

orexinsmacrophages 929neutrophils 929

organ function, loss of 3organogenesis 219organ-specific inflammation 1161organ transplantation 1147, 1313organum vasculosum laminae

terminalis (OVLT) 871orphan type I cytokines 596

G-CSF signals 598orthomyxoviridae

5’-Triphosphate ssRNA 34orthopoxviruses 324osteoarthritis (OA) 1674osteoclasts 221, 1115

regulation 598osteomyelitis 1567

Index 1729

osteopontin 918, 1203, 1525outer membrane protein A

(OmPA) 27deficient mutants 27

outer-surface protein A (OspA) 151OVA. see ovalbumin (OVA)ovalbumin (OVA) 292

induced allergic asthma model 662oxidative damage 701

DNA damage 710oxidative injury 916oxidative phosphorylation

(OXPHOS) 954, 1383oxidative metabolism 915

oxidative stress 695, 697, 698, 961,1186, 1212

antioxidant gene expression, roleof 712

biomarkers of 701oxidized LDL (oxLDL) 1283

derived cholesterol 1291OX40 ligand 280OX40L-OX40 536oxygen

delivery 1318diffuses 131hypoxia, cascade demonstrating levels

of 950sensing 130

transcription factors 133

ppain

basic concepts of 891excitatory mechanisms 892inhibitory mechanisms 895

clinical concepts of 899analgesic drugs 900biopsychosocial concept and

multidisciplinarymanagement 900

translation of basic research intoclinical applications 902

paleopathology 1Pam2Cys lipopeptide 151PAMP. see pathogen-associated

molecular pattern (PAMP)

pandemrix 147paneth cells 438, 439, 441, 446pannexin-1 489panton-valentine leucocidin (PVL) 959paracoccidoides brasiliensis 1353paramyxoviridae

5’-Triphosphate ssRNA 34parasitic infections 1398paraventricular hypothalamus

(PVH) 655paraventricular nucleus (PVN) 1487,

1489Parkinson’s disease 1489paroxysmal nocturnal hemoglobinuria

(PNH) 803PASI 75 scores 555passive ligand 257pathogen, agents targeting 1585pathogen-associated microbial

proteases 743pathogen-associated molecular pattern

(PAMP) 19, 57, 105, 175,223, 275, 654, 791, 821, 862,868, 956, 974, 997, 1032, 1152,1351, 1369, 1423, 1486, 1541,1583, 1585, 1587

agents targeting hostresponses 1589

bacterialDNA 31fimbriae 30flagellin 28glycogolipids 30heat shock proteins 30, 822lipoproteins 26lipoteichoic acid 27peptidoglycan 28RNA 32

CD28 costimulatory signal peptideinhibitors 1598

epithelial membrane barriers 1592extracellular/intracellular signaling

inhibitors 1590fungal 36hemoperfusion systems 1584high mobility group box 1

(HMGB1) 1592

1730 Index

histone inhibitors 1590immune reconstitution

strategies 1596immunomodulators 1595interleukin-1 receptor antagonist

(IL-1ra) 1598mesenchymal stem cells 1596mitochondrial sparing agents 1596parasitic infection 35proresolving agents 1592receptor for advanced glycation end

products (RAGE)inhibitors 1591

recombinant gelsolin 1591statins 1588vascular endothelium in acute

inflammatory states 1594viral PAMPs 33

pathogens 956clearance 785initiated innate immune

responses 58opsonization 787removal 785

patrolling monocytes 219pattern recognition molecule

(PRM) 1349pattern recognition receptor (PRR) 19,

58, 82, 175, 223, 275, 441, 996,1237, 1281, 1369, 1423, 1485,1541, 1588

C-type lectin-like receptor 175distribution 176nucleotide-binding oligomerization

domain (NOD)-likereceptor 175

retinoic acid-inducible gene-1-like(RIG-1) receptor 175

sensing necrotic cells 59toll-like receptor (TLR) 175

PCT. see procalcitonin (PCT)PDE4 inhibitor 1190pellino-3b deactivates IRAK-1 1431pentose phosphate pathway

(PPP) 982pentraxin 3 (PTX3) 1352, 1354,

1542–1544

coated surfaces 1355deficiency 1356deficient mice, in skin and liver

damage 1356deficient remodeling cells 1356general scenario 1349protein 1352resistant mutants 1354

peptide hormones 442peptidoglycan (PGN) 19, 25, 28, 191,

192, 959chemical structure 29peptidoglycan-associated lipoprotein

(PAL) 27peptidoglycan recognition protein

(PGRP) 30peptidyl-arginin deiminase 1108peptidyl isomerases (PPIases) 27periodontitis 1233, 1447peripheral lymphoid organs 677peripheral nerves 1491

injury 676peripheral tolerance 1054perivascular macrophages 918peroxisome proliferative activated

receptor (PPAR) 982, 1227,1390

γ (PPARγ) 106, 231, 446, 668, 705,954, 1205, 1236

activation 1237peroxynitrite (ONOO-) 697, 704, 705,

713, 1265persistent critical illness (PCI) 1592,

1593Peyer’s patches 344, 348, 551, 637, 640

of carvacrol-treated animals 823PGF2α-FP signaling 663PGN. see peptidoglycan (PGN)PGs. See prostaglandins (PGs)phagocytes 5, 6, 262

microglia 1256professional 224

phagocytosed bacteria 791phagocytosis 4, 223–225, 366, 419,

789, 802, 916, 1155, 1307,1544

induced cell death 958

Index 1731

phagosomes 192, 224, 259PHD. see prolyl hydroxylase

dehydrogenase (PHD)phenol-water extraction 26Phoneutria nigriventer venom

causes paralysis 110phorbol-12-myristate-13-acetate

(PMA) 1426phosphatase and tensin homolog

(PTEN)activation 1385catalyze 1382

phosphatidic acid (PA) 671phosphatidic acid-selective

phospholipase A1

(PA-PLA1α) 673phosphatidylinositol 3-kinase

(PI3K) 1230, 1231, 1371,1672

activation 789Akt/mTOR pathway 1385, 1672pathway 1382phosphoinositide 3-kinase γ

(PI3 kinase γ) 635phosphatidylinositol-(3,4,5)-

triphosphate (PIP3) 1381phosphoinositide-dependent kinase 1

(PDK1) 1381phospholipase C dependent 488phospholipases 100, 257

phospholipase A2 (PLA2) 651, 671,869

on membranephospholipids 1672

phospholipase C 635phospholipase D 671

phospholipid cardiolipin 299phospholipomannan 37phosphorylated insulin receptor 1230phosphorylation 195, 259, 366, 813,

1205, 1431phosphorylcholine (PC) 1353phytohemagglutin (PHA) 483pioglitazone 1237pituitary gland (PitG) 1488pituitary hormones 920

arginine vasopressin (AVP) 920

lymphocytes, and macrophages 920NK cells 920

placental growth factor (PlGF) 466plasmacytoid dendritic cell (pDC) 156,

599, 1092, 1112derived IFN-α 1096

plasmacytomas 1366plasma kallikrein-kinin system 741plasma proteins 457plasminogen activator inhibitor-1 (PAI-1)

expression in endothelial cells 845plasminogen-plasmin system 844Plasmodium cynomolgi 1428Plasmodium falciparum 426plasmodium infection 1398platelets 836

activating factor 619bacteria, interactions 422bacterial endotoxin (LPS)

adherent 422consumption 834human platelets 420, 424and inflammatory disorders 425inflammatory processes 421integrins 424leukocyte aggregates 423, 424leukocyte interactions 423Limulus polyphemus 419membrane glycoprotein (GP)

Ibα 423microparticle 421, 425nonhemostatic components 421platelet-activating factor (PAF) 106platelet-derived growth factor

(PDGF) 467platelet endothelial cell adhesion

molecule-1 (PECAM-1) 257,466, 1203

recruitment 463role in immune responses 425signaling 426toll-like receptors, expression

of 422white blood cells, interactions 423

PLCγ cleaves phosphatidylinositolbisphosphate (PIP2) 1666

pleckstrin-homology domains 1381

1732 Index

pleiotropy 573Pneumocystis carinii 182pneumolysin 83podocytes 799, 800polarization 627poliovirus 178polyangiitis 264polyclonal 1151polyglycolic acid (PGA) 1677polyinosinic-polycytidylic acid

(poly I:C) 60, 152, 1426polyketides 1676polymorphic protein-1 (PMP-1) 422polymorphisms 177, 185, 1120polymorphonuclear (PMN)

infiltration 1452leukocyte (PML) 423, 791, 1447

poly lactic-co-glycolic acid(PLGA) 1677

polysaccharidic moiety 22polyubiquitination 192Porphyromonas gingivalis LPS 1426positron emission tomography

(PET) 1257, 1568post-translational modifications 789,

954power Doppler ultrasound

(PDUS) 1580Poxviridae family 324p50p65 NF-κB heterodimer 1431preadipocytes 1205, 1228preepigenetic sensing, and

signaling 974preimmunization 819preoptic area (POA) 655, 864presepsin (soluble CD14

subtype) 1547p70 ribosomal protein S6 kinase 1

(S6K1) 1384primary lymphoid organs, and

chemokines 636primary percutaneous coronary

intervention (PCI) 1318PRL. see prolactin (PRL)proapoptotic signaling 529procalcitonin (PCT) 1542, 1544

guided algorithms 1545

induction 1544levels 1544production 1544values 1545

progesteronereduce NK cell activity 919suppresses antibody production 920

programmed cell death protein 1(PD1) 1163

proinflammatorycytokines 37, 60, 188, 193, 223, 505,

592, 654, 788, 815, 838, 842,920, 1315

responses 1498genes 179, 180, 658and immunoregulatory factors 341leukocyte influx 1523mediators 557T cells 1228

T helper 17 cells 1367prolactin (PRL) 921proliferation 457

signals 592prolyl hydroxylase dehydrogenase

(PHD) 134enzymes 1320on HIF 132inhibitors 1320

promyelocytic leukemia zinc finger(PLZF) 343

Propionibacterium acnes 491, 1426proprotein convertase subtilisin kexin 9

(PCSK9) 1592proresolving lipid mediators, in

resolution of acuteinflammation 1448

prostaglandins (PGs) 102, 229, 348,619, 651, 654, 917, 1449

anti-inflammatory actions 663autoimmune and allergic

inflammation, role in 659as cytokine amplifiers 657degrading enzyme 664positive feedback loops of

inflammation, role in 657prostacyclin (PGI2) 459, 463

IP pathway 654

Index 1733

prostaglandins (PGs) (Continued )mediated amplification 658

prostaglandin E2 862, 964CXCL1 pathway 659EP2 signaling 658EP3 signaling 662EP4 signaling 657, 659induced edema formation 654in MnPO, role of 874

prostaglandin E synthase 869prostaglandin H2 459receptors for 669roles in nervous system 656, 657Th2-mediated allergic inflammation,

role in 661Th1/Th17-mediated autoimmune

inflammation, role in 660tissue remodeling 663

prosthetic valve 1567protease-activated receptor

(PAR) 734, 997, 1595activation on cells, inflammation-

related effects of 737proteases 732, 736

hyperactivity 727inhibitors 729, 1350as targets in inflammatory

pathologies 747airways 748gut 747joints 751pancreatitis 752skin 750traumatic brain injury 752

proteasome 192protectin 1452

protectin D1 (PD1) 1498protective antigen (PA) 84protein

alterations 813docking, computer algorithms 1676folding 88modifications 814structure 1352synthesis 1385

proteinases 727proteinase-3 732, 734

protein C 1316activation 839pathway 838system 837, 839, 844

protein kinases 1666dependent signal transduction 589protein kinase A 655protein kinase C 186, 635, 655, 789,

960, 1230, 1666γ-isoform 676

protein kinase G 702proteolysis 577, 1549proteolytic

activity 727, 733cleavage 787

proteomics 100prothrombin time (PT) 834prothrombotic state 837protocadherin (PCDH1) 999protocatechuic acid 1288Protonectarina sylveirae venoms

112proximity ligation assay (PLA) 502PRR. see pattern recognition receptor

(PRR)Pseudomonas aeruginosa 4, 191, 706,

959psoriasis 1092

anti-IL-17 therapy in 554area and severity index 554, 1097psoriatic arthritis 555, 1116clinical and histological

features 1093molecular features 1092

guttate 1094immunopathogenesis 1091lesions 1093plaque 1094pustular 1094skin 1093

adaptive immune responses 1096biopsy 1093dendritic cells interplaying with

T cells 1096IL-12p40 1097IL-23/TH17 1098inflammation 1094, 1095

1734 Index

inflammatory molecules fortargeted treatment 1097

keratinocytes triggeringinnate 1096

neutrophils 1097T cells 1094TNF-α 1098

skin lesions 1096vulgaris 1091, 1094

PTEN. see phosphatase and tensinhomolog (PTEN)

PTX3. see pentraxin 3 (PTX3)pulmonary edema, acute 107pulmonary embolism (PE) 464pulmonary fibrosis 347putative proteinase maturation protein

A (PpmA) 27putative pyrogens, possible sites of

action for 864P2X7 receptor 957

Glu496Ala loss 489pyocyanic bacillus 4pyocyanin 959pyrin domain (PYD) 1370pyrogenic cytokines 868pyrogens 874

interfere 864pyrogenic zone 865

pyroptosis 138, 195pyrotoxina 4, 21

qquantitative D-dimer assay 846Quillaia saponins 148

rRA. see rheumatoid arthritis (RA)RAG-complementation analyses 1382Rag-independent innate

lymphocytes 316RANK ligand 344, 1110, 1115rapamycin 794Raphe pallidum neurons 655rapid signal transfer 873rapid thermoregulatory responses 864RAS/MAPK pathways 593, 1230RC-529 adjuvanted vaccines 154

reactive free radical 710reactive nitrogen species (RNS) 697,

702anti-infectious agents, as 705general properties 698metabolism 704

reactive oxygen species (ROS) 104,132, 175, 260, 278, 695, 697,700, 791, 815, 916, 1177, 1189,1205, 1258, 1314, 1522

biomarkers of 701general properties 698redox interconversion of 708

reactive sulfur species (RSS) 706general properties 698

receptor 4-1BB 533receptor for advanced glycation

end-products (RAGE) 60,1518

receptor for hyaluronan-mediatedmotility (RHAMM) 1154

receptor interaction protein (RIP) 180receptor retinoic acid (RA) 341receptor tyrosine kinase signal

transduction 465recombinant human APC

(rhAPC) 840redox code 697, 698

health and disease, use in 713principles 699

redox diseases 713redox-related switch-off signal 713regulatory T cells (Treg) 292, 299,

366, 395, 407, 505, 640, 819,1094, 1203, 1212, 1377, 1423,1524

accumulation 1204adipose tissue 1389canonical genes 1380clinical perspectives 1399in context of infections 1394depletion 1396effector 1386intestinal 1390molecular mechanisms 1380natural Tregs (nTregs) 1060nonlymphoid tissue-resident 1389

Index 1735

peripheral-induced 1390populations 1388subpopulations 1379subsets 1060suppressor 1377, 1378thymus-derived vs. peripherally

derived 1379rejection, chronic 1159renal

allografts 1154biopsies, human 800blood flow (RBF) 1302, 1303damage 1320dysfunction 802, 803isografts 1154response to systemic

inflammation 1304changes in renal

hemodynamics 1307endothelial activation 1304glomerular filtration barrier

changes 1305tubular injury 1306

transplantation 1320vasodilation 1307

renin-angiotensin-system (RAS) 1235aldosterone system 915

reperfusion 263, 1155, 1314reprogramming 1428resistin 926

resistin-like molecule β(RELMβ) 345

resolvin D1 (RvD1)RvD1 1454

resolvin E1 (RvE1) 1451RvE1 formation 1452RvE1 signals 1452

respiratory burst 713respiratory syncytial virus (RSV) 34resveratrol (RES) 1211reticulo-endothelial system 5retinoic acid-inducible gene-I

(RIG-I) 32, 62receptors 1315, 1541

retinoid acid-related orphan receptor(ROR) 549

alpha 315

gamma 397retinopathies 230reverse cholesterol transport

(RCT) 1280reverse pharmacology 1662rhabdoviridae

5’-Triphosphate ssRNA 34rheumatoid arthritis (RA) 65, 263,

496, 530, 578, 659, 792, 918,1105, 1106, 1392, 1488, 1671,1674

clinical phenotype 1106endothelial cells 1111etiology 1106fibroblast-like synoviocytes 1109inflammatory cells and mediators

driving 1109innate immunity and stromal

cells 1109innate lymphoid cells 1111monocytes and macrophages 1110neutrophils and mast cells 1111structural changes in

cartilage damage and boneerosions 1115

rhinosinusitis, chronic, associated withnasal polyps 347

rhodopsin-like family of GPCRs 632Rho GTPases family 87RIG-I-like receptors (RLRs) 137,

187–188, 997, 1369signaling 188, 189

rituximab 802RNA

derived markers 1552ribosomal 1385

single-stranded (ssRNA) 178RNase A-type ribonucleases 66RNS. see reactive nitrogen species

(RNS)RORc expression 404ROS. see reactive oxygen species (ROS)Ross River virus 1354rostral raphe pallidus nucleus

(rRPa) 865rostroventrolateral medulla

(RVM) 1487, 1490

1736 Index

rotational thrombelastography(ROTEM) 846

sS. agalatiae 423salivary gland (SVG) 320Salmonella enterica 30, 1354Salmonella typhi 917Salmonella typhimurium 83, 192, 957,

1353Salmonella typhosa 1423salsalate 1211SAP. see serum amyloid P (SAP)sarcoidosis 1576scavenger cells 788

macrophages 788monocytes 788neutrophils 788

scavenger receptors 1281class A (SR-A) 1280

sCD40 ligand 466schistocytes 800Schistosoma mansoni 36, 420, 1398

egg 36Schwartzman reaction 21scorpion Leiurus quinquestriatus 106scorpion venoms

inflammation induced 105–107inflammatory action, schematic

representation of 108SEB-induced toxic shock 1590secondary lymphoid organ (SLO) 637secretory mucin-containing

granules 440Secukinumab 408, 553–556segmented filamentous bacterium

(SFB) 551selectins (Sel) 1518

E-selectin 280, 461, 1154P-selectin 462, 1154

dependent reaction 836glycoprotein ligand-1

(PSGL-1) 256, 957, 1154selective PPAR-γ modulators

(SPPARMs) 1237self-induced ligands 184self-nucleic acids 178

seminal experiments 1392senescence 1189sense perturbations 131sensitization 999

phase 996sensory circumventricular organs

(sensory Cvos) 871sensory neurons 1493sepsis 795, 947, 1031, 1331, 1488,

1542acute mortality 1032clinical management 1037DAMPs 1033dendritic cells 1035epidemiology 1031

incidence 1031host immune response 1032illness concepts updated definitions

and clinical criterialimitations of previous

definitions 1037Sepsis-3 1037, 1038

immune cell abnormalities in 1034induced mortality 177lymphocytes 1035macrophages 1034mechanisms of organ dysfunction

in 1037metabolic alterations in 1036mitochondrial function in 1036monocytes 1034natural killer cells 1035and neutrophils 1034pattern recognition receptor 1033polymicrobial 795, 798, 803transduction of danger signals

1033Sepsis-related Organ Failure

Assessment score (SOFAscore) 1038

septic shock 1038serine and threonine kinases 1231serine proteases 786, 1316serine-rich repeat (Srr) 423serine/threonine kinase protein kinase B

(PKB/Akt) 1381serine/threonine-phosphorylation 1231

Index 1737

serotonin 1497producing enterochromaffin cells 442

Serratia marcescens 8, 21serum albumin 711serum amyloid A (SAA) 965, 1282serum amyloid P (SAP) 1352

component 1349deficient mice 1355protomers 1351

serum sickness 995serum therapy 1584severe sepsis-induced ADAMTS13

deficiency 837sex hormones 918sexual dimorphism 918SH1-containing inositol-5´ phosphatase

(SHIP-1) 1430Shiga toxins (Stxs) 88Shigella dysenteriae 1424Shigella infection 801SHIP-deficient mice 1383short consensus repeat (SCR) 788short-hairpin 1454sialic acid 323

binding immunoglobulin-like lectin9 1579

sickness behaviors 861encompasses fever 1494

sickness-induced lethargy 657signaling chains 589signal regulatory protein-alpha

(SIRPα) 225signal transducer and activator of

transcription (STAT)pathway 366, 963, 1097

signal transduction 587–589, 596, 600,634

signal transducers 921signal transducing receptor 573

silent mating-type informationregulator-2 (Sir2) 983

single IgG domain of IL-18BP is similarto IL-1R8 (SIGIRR) 496

single-nucleotide polymorphism(SNP) 661, 1329, 1331

for acute and chronic inflammatorydisorders 1342

associated with susceptibility to thedevelopment of sepsis 1332

and functional genomics 1330homozygosity 1339selection of 1331

single photon-emission computedtomography (SPECT) 1568,1572

Singleton-Merten syndrome 188siRNA treatment targeting

HMGB1 60Sirt1 epigenetic-based homeostat for sepsis

inflammation treatment 986sirtuins 983

in inflammation 984Sjogren’s syndrome 329skin

associated lymphoid tissue 1091homing immunity 1092homing T cells 1091immunity and chemokines 641inflammation

T-helper subtypes 1093keratinocytes 484

SLE. see systemic lupus erythematosus(SLE)

sleep disturbance 861Smad3 protein 507α-smooth muscle actin (α-SMA) 675,

1526smooth muscle cell (SMC) 791snakebite envenoming constitutes 100snake venoms

induced edema 101inflammation 99–105proteomics 100

SOD. see superoxide dismutase (SOD)soluble decoy TLRs 1371soluble egg antigen (SEA) 36soluble mediators 370soluble triggering receptor expressed on

myeloid cells-1(sTREM-1) 1548

soluble urokinase-type plasminogenactivator receptor(suPAR) 1549

levels 1549

1738 Index

specialized proresolving mediators(SPM) 965, 1448, 1488

specific receptors and biologicalactions 1450, 1457

sphingosine (Sph) 673sphingosine-1-phosphate (S1P) 667

receptor 637, 670, 671, 1524structure 668synthetic

degrading, and action of 672pathways 673

sphingosylphosphorylcholine(SPC) 673

spidersbrown 108venoms

inflammation induced 107–110spinal protein kinases pathways 112spleen tyrosine kinase (Syk) 183spondyloarthritis 1116

adaptive immunity 1119bone remodeling in 1121cells and mediators driving 1117clinical phenotype 1116cross-talk between innate and

adaptive immunity 1118dendritic cell (DC) 1119iNKT cell 1119MAIT cells 1119γδT cells 1119

etiology 1116innate immunity and stromal

cells 1117endothelial cells 1118fibroblast-like synoviocytes 1117innate lymphoid cells 1118monocytes and

macrophages 1117neutrophils and mast cells 1118

spondyloarthritis (SpA) 1105S100 proteins 1092Src homology 2 domain-containing

inositol-5-phosphatase(SHIP1) 1382

Src inhibition 469Src-kinase tyrosine

phosphorylation 469

SRR adhesins 423Staphyloccocus aureus 83, 326, 422,

732pore-forming toxin 959

Staphylococcus epidermidis 31, 486,1575

starfish larvae 4statin-induced 13-series

resolvins 1457STAT proteins 366

STAT1, activation 596STAT3

deficient TREGS 1388dependent mechanism 550protein 404signal transduction 595

sterileliver 1356

steroidshormones 917natural/synthetic, relative potencies

of 1471sterol regulatory element-binding

protein (SREBP) 1384Streptococcus

group B Streptococcus (GBS) 83Streptococcus agalactiae 83Streptococcus pneumoniae 10, 83,

191, 420, 732, 1179, 1353Streptococcus pyogenes 21, 1353,

1426stress responses 815stroke 1280stromal cells 591stromal vascular fraction (SVF) 1199

cells 1200Strongyloides venezuelensis 345SubAB-mediated suppression 89subcapsular sinus (SCS) 226subfornical organ (SFO) 871substance P (SP) 110subtilase cytotoxin (SubAB) 89successive redox reactions 699succinate 954sulfhydryl

free groups 709sulfur-based radicals 706

Index 1739

sulfur-containing amino acids 707sulfur oxidases (SOX) 707superantigens 1068superoxide 459, 700superoxide dismutase (SOD) 137, 696,

916, 1319SOD1 1264SOD3 1186

suppressor-of-cytokine signaling(SOCS) 232, 1371, 1523

surface markers 370surfactant proteins 734

protein D 182Surviving Sepsis Campaign

(SSC) 1037synaptic plasticity 767synthetic dipalmitoylated

lipopeptide 27systemic autoimmunity 1388systemic hypotension, sepsis-

induced 1307systemic inflammatory response 836,

1200, 1583, 1597syndrome 106, 1037, 1301, 1428

systemic lupus erythematosus(SLE) 186, 426, 792, 802,995, 1054, 1392, 1476, 1674

aberrant cell death 1075adjuvant mimicry leading to

pseudoantiviralimmunity 1075

autoreactive lymphocyteclones 1076

environmental factors promotingsystemic lupus erythematosusactivity 1076

erythematosus 580pathomechanisms 1075

systemic onset juvenile arthritis(sJIA) 497

systems pharmacology 1676

ttachykinin NK1 receptors 111tacrolimus 1673TANK-binding kinase 1 (TBK1) 180T-bet 341, 366, 406

T-bet+ ILC3s 344T-box transcription factor 366T-cell 61, 280, 315, 341, 342, 396, 533,

536, 539, 629, 633, 638, 639,785, 921, 947, 954, 971, 1150,1151, 1228, 1279, 1316, 1343

anergy 299autoantigen 1097clonal deletion of 1056clones 365compartments 1154effector and regulatory 529factor 1 (TCF-1) 342growth factor 590immunity 792immunoglobulin domain and mucin

domain 3 (TIM3) 1431mediated inflammatory

disease 1099memory 529Naïve T cells 289polarization 365receptor 637, 659, 1004, 1056,

1076, 1666induced clonal deletion 1379induced expression of members of

the TNF superfamily(TNFSF) 1385

ligation 1384signaling 366transgenic mice 1059

suppression 226transfer 460vaccination 819

Tconv cells 299tertiary lymphoid organs (TLOs) 1072testosterone, reducing TLR-4

expression by macrophageand monocytes 919

tetanus toxoid vaccine 146tetrahydrobiopterin (BH4) 703TF. see tissue factor (TF)T follicular helper cells 366Th1 cell 365, 366, 639, 659

cytokines 469IL-1-β 103

differentiation

1740 Index

PGE2-EP2/EP4-mediatedfacilitation, role of 661

effector CD4+ T cells 299master regulator transcription

factor 639mediated signals 553polarization 1097

Th2 cell 365, 366, 634, 659, 996, 1203cytokines 469, 558, 665, 1070

response 496differentiation 374driven allergic-induced asthma 559immunity 293mediated allergic inflammation 366,

663produced IL-5 increased circulating

eosinophils 366TH2-associated innate and adaptive

immunity 345Th9 cell 375

associated cytokines andchemokines 371

associated effector molecules 381differentiation 374, 377

cytokines and costimulatorsrequired fordifferentiation 377

Th9 biology, factors required forpromotion of 380

transcription factors fordifferentiation 379

in disease helpful and unhelpful 371driven allergic-induced asthma 559function of 369inducing

cell surface ligands 369cytokines, additional 368

introduction to 367responses, therapies potentially

beneficial in modulating 378targeting therapeutically 377

Th17 cell 395, 396, 551, 555, 640, 659,1475

during chronic inflammation 405clinical targeting of 407cytokines acting on 401

IL-23 401

IL-27 401cytokines and chemokines produced

by 399CCL20 400IL-21 400IL-22 400IL-17A and IL-17F 399

differentiation of 396circulating vs. tissue

phenotypes 398in humans 397in mice 396pathogenic Th17 cells 398

effector CD4+ T cells 299and inflammatory diseases 401

arthritic diseases 402inflammatory bowel diseases 403multiple sclerosis 403psoriasis 402TH17-associated cytokines 341,

344phenotypes 399

during chronic inflammation,differentiation, recruitment,and maintenance of 403

plasticity of 405, 406polarization 1092

T-helper cell 341, 1094lineage memory cells 591subtype participation in

autoimmunity 595therapeutic interventions 1210, 1265thermal hyperalgesia 655thermoafferent pathway 865thermoregulatory 863

effectors 863system 863thresholds 864

thermosensors 864thiazolidinediones (TZDs) 1210

adipose effects of 1236insulin sensitizing effect 1236

thioredoxin (TRX) 138thiyl radicals (R-S•) 706threonine amino acid residues 440threshold temperatures 863thrombelastography (TEG) 846

Index 1741

thrombin 733, 1595activatable fibrinolysis inhibitor

(TAFI) 840thrombocytopenia 425, 426, 800, 995thrombocytosis 425thrombolysis agent 1317thrombomodulin (TM) 840, 1590

bound thrombin 841TM-1 1525

thrombotic microangiopathies 801thromboxane A2 (TxA2) 459

induced vasoconstriction 461synthase 460TP signaling 663

Thr308, phosphorylation of 1381Thr37 residue of Rho 88thymic DC 1062thymic regulatory T cells (tTreg) 298,

1378thymic self-ligands 1378thymic stromal lymphopoietin

(TSLP) 996thymocytes 224thymus 1057, 1065

derived TREGS (tTREGS) 1379thyroid hormones 915, 916thyroxine (T4; 3,5,3´,5´-

tetraiodothyronine) 915tie-2-mediated phosphorylation 467timeline of autoantibody-positive

rheumatoid arthritis(RA) 1108

TIR. see toll-interleukin receptor (TIR)TIR-containing adapter protein

(TIRAP) 1370tissue damage 787, 915, 1363tissue factor (TF) 464

eomesodermin 341inhibitors 1316pathway inhibitor 732, 837protease inhibitor (TFPI) 739, 841

tissue ILCs homeostasis 345tissue inhibitor of metalloproteinase 1

(TIMP1) 1208tissue injury 629tissue metaplasia 663tissue remodeling 663

tissue repair 1355, 1517anti-inflammatory cytokines 1523cellular effectors of resolution 1524chemokines regulate leukocyte

recruitment 1520complement cascade 1519extracellular matrix 1525fibroblast activation/scar

formation 1526inflammatory response 1517leukocyte adhesion cascade 1523leukocyte recruitment 1521macrophages 1521negative regulation of cytokine

signaling 1523pathways 790postinfarction inflammation 1523proinflammatory cytokines 1519repression/resolution of

inflammation 1522role of neutrophils 1522tissue-specific events leading to

regeneration 1525Tityus serrulatus venom 106TL1A/DR3 interaction 534TLR. see toll-like receptors (TLR)TNF. see tumor necrosis factor (TNF)tocilizumab 407, 580, 1343tofacitinib 1343tolerance 1159

and accommodation of blood groupmismatched transplants 1160

tolerogenic dendritic cells 596, 825,1062

toll-interleukin receptor (TIR) 479,1430, 1590

toll interleukin-1 receptor domain-containing adapter-inducinginterferon-β (TRIF)pathway 59

toll-like receptors (TLR) 24, 105, 138,150, 176–181, 220, 275, 441,468, 551, 594, 796, 821, 974,997, 1097, 1152, 1232, 1281,1282, 1315, 1351, 1423, 1488,1518, 1541, 1590, 1664

agonists 144

1742 Index

cell surface-bound TLRs 177endosomal TLRs 178humans TLR4 expression 1153ligands 145, 296, 479, 602, 916MyD88-dependent signaling

pathway 179signaling 601

pathway 1370, 1371signaling pathway 180TLR signaling 179TLR2 34, 58, 151, 1426, 1474

mediated cell activation 34stimulation 1264

TLR3 152, 153ligands/immunogenicity 152dependent signaling 1264

TLR4 153deficient mice 64inhibitors 1320MyD88 signaling pathway 105,

1353TLR5 154TLR 7/8 154, 155

tolerizes cells 1426TLR9 156, 157

agonist CpG ODN 147clinical activity 156ligands 156safety 157transfected HEK cells 31

TRIF signaling pathway 179vaccine adjuvants targeting

clinical activity 151, 153, 155innate immune system 150safety 152–155

toxins blocking protein synthesis 88Toxoplasma gondii 36, 178, 768, 1426TOX protein 342traditional Chinese medicine

(TCM) 1661transcription activators 532, 921transcription factors 315, 341, 366,

395, 1315transforming growth factor

(TGF) 262, 549, 734, 1328,1385

TGF β 467, 676, 1368

activated kinase 179, 1385, 1430TGFβ/BMP signaling 1121

transgenic mice expressing humanIL-37 (IL37-tg) 501

transient receptor potential V1(TRPV1) 668

transit-amplifying cell (TAC) 438transmembrane activator calcium

modulator 536transplantation 1203

modulating inflammation toimprove 1163

treatment 1162azathioprine 1162CTLA4-Ig 1163cyclosporine A 1162monoclonal antibodies 1163

Δ10-trans-RvD2 isomer 1456transsulfuration pathway 707traumatic brain injury 1150Treg. see regulatory T cells (Treg)trehalose dimycolate (TDM) 185triacylated lipopetide 25Trichuris muris 345, 558trigeminal nerve 864triggering receptor expressed

on myeloid cells-1(TREM-1) 38, 1548, 1591

upregulated expression 1548triglycerides 1207, 1227trimethylamine-N-oxide

(TMAO) 1288trinitrobenzene sulfonic acid

(TNBS) 552, 661induced colitis 494

Tripterygium wilfordii 1677Tripterygium wilfordii Hook F 1674TRX interacting protein (TXNIP) 138Trypanosoma cruzi 550

infections 35trypanosomatidae DNAs 62TSH administration 916T suppressor cells 1377tuberous sclerosis complex (TSC) 1381tubular cell apoptosis 1307tubulin 818tubulointerstitial fibrosis (TIF) 676

Index 1743

tumorantigen MAGE-3 157associated macrophages 229immunity 372progression 220regression 235, 1394

tumor necrosis factor (TNF) 21, 103,109, 274, 397, 530, 732, 768,791, 834, 837, 862, 1000, 1096,1176, 1199, 1330, 1425, 1428,1519, 1543

biological roles 530converting enzyme (TACE) 34, 530gene 1330

molecule, characterization of 532IFN-γ 1228immunoblockade 465induced gene expression 658mechanisms of action 531promoter 1338related apoptosis-inducing ligand

receptor 1371role in neuronal inflammation 538role on inflammatory bowel

diseases 537signaling 1590soluble 530superfamily

actions of 531members 540

synthesis 1520tumor necrosis factor receptor

(TNFR) 529, 530, 532,1385

associated factor 550interactions 538superfamily 529, 532

BAFF-R-BAFF 536DcR3 535Fas ligands 534GITRL 537OX40 or ACT35 or CD134 or

TNFRSF4 536TL1A 533TRAIL 535TWEAK 535

TNFR-1 531

TNFR-associated death domain(TRADD) 529

TNFR-associated factor(TRAF) 1371, 1430

TNFRSF interactions 538TNFRSF1B encoding

receptor 1331TxA2. see thromboxane A2 (TxA2)typhoid vaccine 4tyrosine 186

autophosphorylation 1231phosphorylation 1230, 1231

uubiquitin E3 ligase 822ulcerative colitis (UC) 374, 400, 457,

460, 537, 540, 1336ultrasound 1573ultraviolet and/or ionizing

radiation 696uncoupling proteins 699unfolded protein response (UPR) 89unilateral ureteral obstruction

(UUO) 675uric acid 185, 711ustekinumab 352, 407, 555uveitis 499UV-inactivated virus 11UV-treated fibroblasts 63

vvaccination

with HSP60-derived peptidep227 824

immunogenicity 143against tumor antigens 1394target toll-like receptors 150

clinical activity 151, 153, 155innate immune system 150safety 152–155, 157TLR2 151TLR3 ligands/

immunogenicity 152TLR4 153TLR5 154TLR7/8 154, 155TLR 9 156

1744 Index

vaccinia virus (VV) 317vagus nerve 864

stimulation (VNS) 1491valine 46 503vascular adhesion protein 1 792, 1578vascular cell adhesion molecule 1

(VCAM-1) 1207, 1474vascular disease, in type 2

diabetes 1234vascular endothelial (VE)

cadherin (cadherin-5) 469vascular endothelial growth factor

(VEGF) 109, 220, 274, 465,657, 1118, 1428

depleting antibodies 465proteolytic modification 466receptor 466receptor 2 468

activity 467VEGF-A isoforms 466VEGF-A-mediated angiogenic

signaling 468VEGF/VEGFR complexes 466

vascularization 636vasculitis 792, 799, 802, 1567, 1575

detected by [18F]FDG PET/CT 1576lesions of 799

vasoactive intestinal peptide(VIP) 1496

vasodilation 112vasomotor dysfunction 458–460

angiogenesis/vasculogenesis 465endothelial cell-dependent

vasoactivity 459endothelium-dependent vasoactivity

in IBD 460enhanced thrombosis 463junctional 468leukocyte–endothelial cell

adhesion 461vascular smooth muscle contraction/

relaxation 459VEGF. see vascular endothelial growth

factor (VEGF)venom-induced inflammation 99venomous animals 99

scorpions 105

venous congestion 1308ventilator-associated pneumonia

(VAP) 1335vesicular stomatitis virus (VSV) 34vespids

inflammation induced byvenoms 110–111

venoms 111vessel wall inflammation,

chronic 792Vibrio cholerae 83

vaccine 146Viperidae family 100viral IL-6 575viral IL-18BP, natural

neutralization 497viral infections 1395, 1398virosomes, nano/microparticles 148virtual screening 1676virulence factors 1584virus-associated inflammatory PD

models 1260virus-induced

immunopathology 1396visceral adipose tissue (VAT) 322,

1389endothelial cells 1205

visceral epithelial cell (VEC) 800visceral fat 1226visfatin 926vitamin A deficiency 347vitamin C (ascorbic acid) 710vitamin D 347vitamin D3 (1,25-dihydroxyvitamin

D3) 825vitamin K deficiency 846von Hippel–Lindau protein

(VHLP) 134tumor suppressor gene 134

von Willebrand factor 836, 845, 1154cleaving protease 837

wWarburg effect 135, 1383warts, hypogammaglobulinemia,

infections, and myelokathexis(WHIM) syndrome 636

Index 1745

Waterhouse-Friderichsensyndrome 833

WEHI164 clone 532Weibel-Palade storage granules 1154West Nile virus (WNV) 317white adipose tissue (WAT) 922

mast cells 1204Willebrand factor 836

multimers 1595Willow tree 1672Wnt agonist R-spondin-1 444Wnt/beta-catenin 1212

signaling pathway 538Wnt inhibitory factor (WIF) 444Wnt-receptor complex 443Wnt signaling 444

pathway 438

wound healing, resolution of 1455WSXWS amino acid motif 598

xxanthine oxidase 700, 716, 976, 1314XIAP gene mutations 497Xigris 796

yyellow fever virus 33

zzeta chain-associated protein kinase 70

(Zap70) deficiency 1065zinc metalloproteinase (Zmp) 957zonula occludens (ZO) 469, 733zymosan-induced peritonitis 1498

1746 Index