Interferons & interleukines

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An antiviral substance & is the first line of defence against

viral attacks.

Term ‘interferon’ orginated from the ‘interference’ of this

molecule on virus replication.

Interferons are a family of host coded proteins produced by

cells on induction by viral or non-viral inducers.

Interferons by itself has no direct action on viruses but it acts

on other cells of the same species, rendering them refractory to

viral infection.

INTERFERONS

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Interferons are inactivated by proteolytic enzymes but not by

nucleases or lipases.

They resist heating at 56-60oC for 30-60mins & stable over a

range of pH 2-10, except gamma IFN which is liable at pH 2.

Mol.wt of 17000 Da - non dialysable & non-sedimentable.

Poorly antigenic, so no routine tests are available for their

detection & estimation.

Interferon assay-based on its biological activity, such as ability

to inhibit plaque formation by sensitive virus.

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Potency of IFN is expressed as International Units(IU) per mL.

Interferons are non-toxic, non-antigenic, diffuses freely in the

body & has a wide spectrum of antiviral activity.

So it is an ideal candidate for use in prophylaxis & treatment of

viral infection.

Interferons are stored at 2 – 8°c

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Proteins in nature & many of them are glycoproteins.

Broadly classified into 3 groups- structure & function.

INTERFERONS

Interferon-α

(INF-α)

Interferon-β

(INF-β)

Interferon-γ

(INF-γ)

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Alpha interferon

• Also known as Leukocyte interferon.

• Produced by leukocytes following induction by suitable

viruses.

• Non-glycosylated protein.

• Atleast 16 antigenic subtypes have been identified.

Beta interferon

• Fibroblast interferon.

• Produced by fibroblasts & epithelial cells following stimulation

by viruses or polynucleotides.

• Is a glycoproteins.

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Gamma interferon

• Immune interferon

• Produced by T-lymphocytes on stimulation by antigens or

mitogens.

• Is a glycoprotein.

• More concerned with immunomodulatory & antiproliferative

functions than with antiviral defence.

• It also differs from alpha & beta interferons in having a

separate cell receptor.

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GENERAL ACTION OF INTERFERONS

Tissue cell is infected by a virus

Releases interferon

Interferon will diffuse to the surrounding

cells & binds with receptor.

Production of a protein that prevents the

synthesis of viral proteins.

Prevents the spread of the virus

throughout the body.

PRODUCTION OF RECOMBINANT

INTERFERONS

The complementary DNA(cDNA) was synthesized from mRNA

of a specific interferon.

Inserted to a vector(plasmid) which is introduced into E.coli or

other cells.

IFN can be isolated from culture medium. This is the basic

mechanism of producing recombinant IFNs.

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THERAPEUTIC APPLICATION OF IFNs

Used for treatment of a large no:of viral diseases & cancers.

Alpha IFNs Hepatitis B & C, chronic myeloid leukemia,

multiple myeloma, Kaposi’s sarcoma, melanoma.

Beta IFNs Multiple sclerosis

Gamma IFNs Chronic granulomatous disease, renal cell

carcinoma, chronic myeloid leukemia.

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IFNs cause the death of cancerous cells by stimulating the

action of natural killer(NK) cells, a specialized form of

lymphocytes that can destroy cancer cells.

Also used for the treatment of common cold & influenza. For

this purpose, IFNs can be used as nasal sprays.

Common side effects of IFNs fever, malaise, fatigue,

muscle pains. High levels of IFNs cause kidney, liver, bone

marrow & heart toxicity.11

MARKETED FORMULATIONS

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BRAND NAME TYPE USE

Alferon N Human leukocyte–

derived interferon alfa-

n3

Genital and perianal

warts

Roferon-A Recombinant interferon

alfa-2a

Hairy cell

leukemia,AIDS

Intron A Recombinant interferon

alfa-2b

Hairy cell

leukemia,AIDS

Avonex, Rebif Recombinant interferon

beta-1a

Multiple sclerosis

Betaseron Recombinant interferon

beta-1b

Multiple sclerosis

INTERLEUKINES

These are a large group of cytokines produced mainly by T cells,

although some are also produced by mononuclear phagocytes

(or) by tissue cells.

The interleukins were first described as signals for

communication between white blood cells (leuk- from

leukocytes).

Currently, it is well-known that these molecules are produced and

used as signalling molecules in many cells of the body, in

addition to immune cells.

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Interleukins are secreted rapidly in response to an infectious agent,

it travels to its target cell and binds to the receptor molecule on the

cell’s surface that triggers a cascade of signals within the target cell

altering the cell’s behaviour.

Interleukins represent a broad family of cytokines that are made by

hematopoietic cells and act primarily on leukocytes.

Interleukins are stored at 2 – 8°c

There are currently 35 well-known interleukins, however, there are

many more to be found and characterized.

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MECHANISM OF ACTION AND DOSE

Mechanism of action;

Immunotherapy with IL activates cytotoxic T-cell against RCC

Dose and adminstration;

Interleukin administered via intravenous (iv) injection as high

dose (usually defined as 600,000 – 720,000 units/kg).

Lower dosage iv and subcutaneous IL-2 are also prescribed for

kidney cancer.

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TYPES OF INTERLEUKINES

Interleukin Primary Cell Structure Primary Activities

IL –1α/IL-1β Macrophages, NK Cells, B cells

Inflammation

IL-2 T cells Activates T cells

IL-3 T cells Haematopoietic growth factor

IL-4 T cells B cell growth

IL-5 T cells Eosinophil & B cell growth

IL-6 T cell & fibroblasts Inflammation

IL-7 Stromal cells B & T cell growth

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Continued ……

Interleukin Primary Cell Structure Primary Activities

IL-8 Macrophages Chemoattractant for neutrophils

IL-9 Activated T cells T cell growth & Potentiates IgM, IgG & Ig

E

IL-10 B cells, T cells B cell growth / inhibition of cytokine synthesis by T

cells

IL-11 Bone marrow stromal cells

Haematopoietic co-factor

IL-12 Macrophages, B cells Induction of cell mediated immunity

IL-13 T cells B cell growth

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PRODUCTION OF INTERLEUKINES

•Antigen is internalized and

degraded by the macrophages,

processed, and then presented on

the macrophage surface to the

resting T lymphocyte in conjunction

with an MHC molecule.

•Once the T-cell receptor engages the

MHC molecule plus antigen, the T

cell becomes activated and secretes

IL-2, IL-3, IL-4, IL-5, and IL-6.

•Interleukins 2,4, 5, and 6 enable

activated T cells to undergo clonal

expansion.

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THERAPEUTIC APPLICATION OF

INTERLEUKINES

Used to enhance T-cell activation in immunodeficiency

diseases.

Used in the treatment of cancers and other infectious diseases.

Used to reduce graft rejection.

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MARKETED FORMULATIONS

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BRAND NAME TYPE USE

ALDESLEUKIN Recombinant human IL-

2 (rIL-2)

Chronic hepatitis C,

and Chronic hepatitis B

OPRELVEKIN Recombinant human IL-

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Hairy cell

leukemia,AIDS

MUPLESTIM IL-3 Hairy cell

leukemia,AIDS

SIGOSIX IL-6 Multiple sclerosis

CONCLUSION

Interferons(IFN) are cytokines that are responsible for the

activity of the immune system .

Interleukins are biologically active glycoproteins derived

primarily from activated lymphocytes and macrophages.

They mediate their action by binding with high affinity to

receptors which belong to a limited number of structural

families

Immunity are produced mainly by activated macrophages

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REFERENCES

Johnson, Howard M., Fuller W. Bazer, Brian E. Szente, et al. "How

Interferons Fight Disease." Scientific American (May 1994): 68–76.

Meulen, Volkerter, N. Stefan. "Inhibition of Major

Histocompatibility Complex Class II-Dependant Antigen

Presentation by Nutralization of Gamma Interferon Leads to

Breakdown of Resistance against Measles Virus-Induced

Encephalitis." Journal of Virology 75 (2000):1–13.

Seppa, Nathan. "Interferon Delays Multiple

Sclerosis." Science News 158 (November 2000): 280–281.

Interferons and Interferon Therapy, R.Priyanka et al /J. Pharm. Sci.

& Res. Vol. 6(12), 2014, 400-40322

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