Interferons in multiple sclerosis: A review of the evidence

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Abstract

Multiple sclerosis (MS) is an inflammatory demyelinating disease of the central nervous system, characterised clinically by relapses and remissions, and leading eventually to chronic disability. Despite an enormous amount of research, the cause of MS remains unknown; however, pathological, genetic and immunological features have been identified that suggest the disease has an autoimmune basis. Accordingly, current therapy of MS includes corticotrophin or corticocosteroids for acute exacerbations, and more potent immunosuppressive drugs for severe cases unresponsive to steroids. All of these agents can cause serious adverse reactions. There urgent need for immunotherapy that is less toxic, that can be given early and perhaps indefinately and that will prevent relapses and progression of the disease. Our current knowledge of the effects of interferons (IFNs) in MS is based on the results of laboratory research and clinical therapeutic trials carried out over the past decade. Existing evidence points to the conclusion that the effects of the IFNs in MS are mediated by immunoregulatory rather than antiviral or nonspecific mechanisms. Administration of IFN(gamma) increases the exacerbation rate, and IFN(gamma) as well as other cytokines may be involved in the pathogenesis of MS lesions. In contrast, studies of IFN(gamma) show that it tends to inhibit the activity of IFN(gamma) and appears to prevent disease activity. Intrathecal administration of IFNbeta, although effective, is cumbersome and potentially hazardous. A large multicentre placebo-controlled trial of systemic recombinant IFNbeta was recently conducted in the US, and the results of the first 2 years of treatment were considered sufficiently encouraging that an application for licensing was submitted to the Food and Drug Administration in June 1992. If approved, it will be the first new agent licensed for clinical use in MS in over 20 years. The study will continue under double-blind conditions for at least another year, and a second trial of systemic recombinant IFNbeta therapy is also in progress. These studies should provide definitive answers to questions about the role of IFNs in the pathogenesis of MS, as well as the place of recombinant IFNbeta as an effective therapeutic agent.

Author-supplied keywords

  • *immunosuppressive agent/do [Drug Dose]
  • *immunosuppressive agent/dt [Drug Therapy]
  • *immunosuppressive treatment
  • *interferon/do [Drug Dose]
  • *interferon/dt [Drug Therapy]
  • *interferon/to [Drug Toxicity]
  • *multiple sclerosis/dt [Drug Therapy]
  • *multiple sclerosis/et [Etiology]
  • *recombinant beta interferon/ae [Adverse Drug Reac
  • *recombinant beta interferon/do [Drug Dose]
  • *recombinant beta interferon/dt [Drug Therapy]
  • alpha interferon/ae [Adverse Drug Reaction]
  • alpha interferon/dt [Drug Therapy]
  • anorexia/si [Side Effect]
  • autoimmunity
  • beta interferon/ae [Adverse Drug Reaction]
  • beta interferon/dt [Drug Therapy]
  • bone marrow suppression/si [Side Effect]
  • cancer immunotherapy
  • chill/si [Side Effect]
  • chronic granulomatous disease/dt [Drug Therapy]
  • controlled study
  • demyelinating disease/dt [Drug Therapy]
  • drug therapy
  • etiology
  • fatigue/si [Side Effect]
  • fever/si [Side Effect]
  • gamma interferon/ae [Adverse Drug Reaction]
  • gamma interferon/dt [Drug Therapy]
  • gamma interferon/ec [Endogenous Compound]
  • headache/si [Side Effect]
  • hepatitis C/dt [Drug Therapy]
  • human
  • immunoregulation
  • influenza/si [Side Effect]
  • interferon beta serine/ae [Adverse Drug Reaction]
  • interferon beta serine/ct [Clinical Trial]
  • interferon beta serine/dt [Drug Therapy]
  • intramuscular drug administration
  • intrathecal drug administration
  • intravenous drug administration
  • larynx papillomatosis/dt [Drug Therapy]
  • malaise/si [Side Effect]
  • melanoma/dt [Drug Therapy]
  • myalgia/si [Side Effect]
  • nausea/si [Side Effect]
  • neurologic disease/si [Side Effect]
  • nonhodgkin lymphoma/dt [Drug Therapy]
  • priority journal
  • recombinant gamma interferon/dt [Drug Therapy]
  • review
  • subacute sclerosing panencephalitis/dt [Drug Thera
  • subcutaneous drug administration

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