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15 interferons
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Interferons
Prof. Dr. Öner Süzer
www.onersuzer.com
osuzer@istanbul.edu.tr
Last update: 12.11.2009
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Interferons
• Interferons are proteins that are currently grouped
into three families: IFN-α, IFN-β, and IFN-γ.
• The IFN-α and IFN-β families comprise type I IFNs,
ie, acid-stable proteins that act on the same receptor
on target cells.
• IFN-γ, a type II IFN, is acid-labile and acts on a
separate receptor on target cells.
BG Katzung, Basic and Clinical Pharmacology, 10th edition
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Production of Interferons
• Type I IFNs are usually induced by virus infections,
with leukocytes producing IFN-α.
• Fibroblasts and epithelial cells produce IFN-β.
• IFN-γ is usually the product of activated T
lymphocytes.
BG Katzung, Basic and Clinical Pharmacology, 10th edition
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Effects of Interferons
• IFNs interact with cell receptors to produce a wide variety of
effects that depend on the cell and IFN types.
• IFNs, particularly IFN-γ, display immune-enhancing properties,
which include increased antigen presentation and macrophage,
NK cell, and cytotoxic T-lymphocyte activation.
• IFNs also inhibit cell proliferation. In this respect, IFN-α and IFN-
β are more potent than IFN-γ.
• Another striking IFN action is increased expression of MHC
molecules on cell surfaces.
• While all three types of IFN induce MHC class I molecules, only
IFN-γ induces class II expression.
• In glial cells, IFN-β antagonizes this effect and may, in fact,
decrease antigen presentation within the nervous system.
BG Katzung, Basic and Clinical Pharmacology, 10th edition
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Use of Interferons
• IFN-α is approved for the treatment of several neoplasms,
including hairy cell leukemia, chronic myelogenous
leukemia, malignant melanoma, and Kaposi's sarcoma,
and for use in hepatitis B and C infections. It has also
shown activity as an anticancer agent in renal cell
carcinoma, carcinoid syndrome, and T cell leukemia.
• IFN-β is approved for use in relapsing-type multiple
sclerosis.
• IFN-γ is approved for the treatment of chronic
granulomatous disease.
BG Katzung, Basic and Clinical Pharmacology, 10th edition
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Recombinant Interferons I
• Interferon gamma-1b is a recombinant polypeptide
that activates phagocytes and induces their
generation of oxygen metabolites that are toxic to a
number of microorganisms.
• It is indicated to reduce the frequency and severity of
serious infections associated with chronic
granulomatous disease.
• Adverse reactions include fever, headache, rash,
fatigue, GI distress, anorexia, weight loss, myalgia,
and depression.
Goodman and Gilman’s The Pharmacological Basis of Therapeutics, 11th edition
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Recombinant Interferons II
• Interferon beta-1a, a 166-amino acid recombinant
glycoprotein, and interferon beta-1b, a 165-amino
acid recombinant protein, have antiviral and
immunomodulatory properties.
• They are FDA approved for the treatment of relapsing
and relapsing-remitting multiple sclerosis to reduce
the frequency of clinical exacerbations.
• The mechanism of their action in multiple sclerosis is
unclear. Flu-like symptoms (fever, chills, myalgia)
and injection-site reactions have been common
adverse effects.
Goodman and Gilman’s The Pharmacological Basis of Therapeutics, 11th edition
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BG Katzung, Basic and Clinical Pharmacology, 10th edition