Biologic effects of interferons: relevance to multiple sclerosis.
Recombinant interferon beta has established efficacy for relapsing-remitting MS, but the mechanisms of action in the disease are not well understood. Interferons (IFNs) mediate biologic effects by receptor-mediated gene activation. Binding by IFNs to high-affinity surface receptors results in physophorylation and activation of two cytoplasmic tyrosine kinases. This leads to activation of latent transcription factors in cell cytoplasm that translocate to the nucleus, where activated transcriptional elements interact with the interferon-stimulated response element (ISRE), leading to transcription of the interferon-stimulated genes (ISGs). IFN's biologic effects are mediated by function of the ISGs. The biologic effects of IFNs have been classified as antiviral, antiproliferative and immunomodulatory; effects are complex, however, because there are two separate types of IFN, four separate varieties of type I IFN and approximately 30 known interferon-regulated genes. Known effects of IFN that may plausibly relate to therapy efficacy in MS are discussed.
Rudick
R A
RA
Mellen Center for Multiple Sclerosis Treatment and Research, Department of Neurology, Cleveland Clinic Foundation, Ohio, 44106, USA.
Ransohoff
R M
RM
D000970:Antineoplastic Agents / Q000276:immunology / Q000627:therapeutic use*; D006801:Humans; D007372:Interferons / Q000276:immunology / Q000627:therapeutic use*; D009103:Multiple Sclerosis / Q000276:immunology* / Q000628:therapy*
D000970:Antineoplastic Agents; D007372:Interferons