Interferons in multiple sclerosis: warnings from experiences.
Administering or neutralizing a single cytokine is currently considered to represent a promising approach to therapeutic intervention in the immune network in autoimmune diseases. In this article, evidence from animal model experiments is reviewed: intervention in such models can have results opposite to those in the clinical disease; and intended neutralization of a cytokine by the administration of anticytokine antibodies can enhance as well as block in vivo cytokine activity. In experimental autoimmune encephalitis in mice, a model system for multiple sclerosis, administration of interferon gamma (IFN-gamma) was found to reduce disease severity and, concordantly, administration of anti-IFN-gamma antibodies was found to aggravate disease. These experimental data are, however, in sharp contrast to the reports on clinical trials, in which IFN-gamma administration was followed by disease relapses. Administration of a neutralizing anti-interleukin-6 (IL-6) antibody to mice to block in vivo activity of IL-6 resulted in increased rather than decreased serum titers, an effect that was found to be due to formation of immune complexes whose elimination from the body is retarded.
Billiau
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Rega Institute, University of Leuven, Belgium.
D000818:Animals; D000906:Antibodies / Q000627:therapeutic use*; D002986:Clinical Trials as Topic; D006801:Humans; D007371:Interferon-gamma / Q000276:immunology* / Q000627:therapeutic use*; D015850:Interleukin-6 / Q000276:immunology; D051379:Mice; D009103:Multiple Sclerosis / Q000276:immunology* / Q000378:metabolism / Q000628:therapy*; D000093242:Interleukin-6 Inhibitors
D000906:Antibodies; D007371:Interferon-gamma; D015850:Interleukin-6; D000093242:Interleukin-6 Inhibitors