Interferons in multiple sclerosis: warnings from experiences.

Abstract

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.