www.aids2014.org High Ratios of Circulating Pro-Inflammatory Cytokines to Anti-Inflammatory IL-10 Correlate with Regional Brain Atrophy in Chronic Suppressed HIV Infection KJ Kallianpur, M Sakoda, TM Umaki, PJ Norris, SM Keating, JD Barbour, LC Ndhlovu, D Chow, ES Nakasone, CM Shikuma The authors report no conflicts of interest. Hawai'i Cent AID University of Hawai
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www.aids2014.org
High Ratios of Circulating Pro-Inflammatory Cytokines to Anti-Inflammatory IL-10 Correlate with Regional Brain Atrophy in Chronic Suppressed HIV Infection
KJ Kallianpur, M Sakoda, TM Umaki, PJ Norris, SM Keating, JD Barbour, LC Ndhlovu, D Chow, ES Nakasone, CM Shikuma
The authors report no conflicts of interest.
H a w a i ' i C e n t e r f o r A I D SU n i v e r s i t y o f H a w a i ' i - M a n o a
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Background
Cytokine levels increase in HIV infection and predict disease progression, mortality
Inflammatory cytokines may contribute to blood-brain barrier disruption
HIV-associated neurocognitive disorders (HAND)
Brain atrophy, microstructural white matter alterations, subcortical brain injury associated with high plasma MCP-11,2
1Ragin et al, 2006; 2Ragin et al, 2010
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Chronic HIV disease Inflammatory markers (IL-6, IL-8,
TNF-α,…) remain elevated after successful combination antiretroviral therapy (cART)
Plasma cytokines associated with memory performance in HIV1
High circulating cytokine ratios to IL-10 (particularly with co-occurrence of elevated IL-1β or IL-8) may mark brain atrophy in HIV patients on cART
An inflammatory environment characterized by inadequate IL-10 response to elevated pro-inflammatory cytokines may be a key factor in HIV neuropathogenesis and persistence of HAND.
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Additional points
i. IL-1β/IL-10, etc. may reflect the immune status of chronically HIV-infected patients
ii. Pro- to anti-inflammatory cytokine ratios should be studied further as potential markers of disease severity that can supplement traditional assessment
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Grant support: NIH grants R01HL095135, U54RR026136, U54MD007584
Acknowledgments: Sincere thanks to our patients and staff for making this study possible.
Thank you
John A. Burns School of Medicine, University of Hawai’i at Manoa
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Points for discussion
a) Why do multiple cytokine ratios over IL-10 correlate with regional brain volumes but not with NP scores?
b) Any other anti-inflammatory cytokines that should be examined (in pro- to anti-inflammatory ratios)?
c) Can circulating cytokine ratios be used early in disease to identify patients at higher risk of brain atrophy or neurocognitive problems?