Mechanisms of action of interferons and glatiramer acetate in multiple sclerosis.
MS is an immunologically mediated disease, as determined by observation of the response to immunotherapy and the existence of an animal model, experimental autoimmune encephalitis. Interferon (IFN) beta-1b, IFN beta-1a, and glatiramer acetate, the therapies used for relapsing or remitting MS, have mechanisms of action that address the immunologic pathophysiology of MS. The IFNs bind to cell surface-specific receptors, initiating a cascade of signaling pathways that end with the secretion of antiviral, antiproliferative, and immunomodulatory gene products. Glatiramer acetate, a synthetic molecule, inhibits the activation of myelin basic protein-reactive T cells and induces a T-cell repertoire characterized by anti-inflammatory effects. Although the two classes of drugs have some overlapping mechanisms of action, the IFNs rapidly block blood-brain barrier leakage and gadolinium (Gd) enhancement within 2 weeks, whereas glatiramer acetate produces less rapid resolution of Gd-enhanced MRI activity. IFN beta has no direct effects in the CNS, but glatiramer acetate-specific T cells are believed to have access to the CNS, where they can exert anti-inflammatory and possibly neuroprotective effects.
Dhib-Jalbut
Suhayl
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Department of Neurology, University of Maryland School of Medicine, Baltimore VA Medical Center, Baltimore, MD, USA.
D000818:Animals; D001812:Blood-Brain Barrier / Q000187:drug effects; D004359:Drug Therapy, Combination; D000068717:Glatiramer Acetate; D006801:Humans; D007166:Immunosuppressive Agents / Q000009:adverse effects / Q000627:therapeutic use*; D000068556:Interferon beta-1a; D000068576:Interferon beta-1b; D016899:Interferon-beta / Q000009:adverse effects / Q000627:therapeutic use*; D008279:Magnetic Resonance Imaging; D009103:Multiple Sclerosis / Q000188:drug therapy* / Q000276:immunology; D010455:Peptides / Q000009:adverse effects / Q000627:therapeutic use*; D013601:T-Lymphocytes / Q000187:drug effects
D007166:Immunosuppressive Agents; D010455:Peptides; D000068576:Interferon beta-1b; D000068717:Glatiramer Acetate; D016899:Interferon-beta; D000068556:Interferon beta-1a