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Keywords:

  • Interferon-γ;
  • Chronic relapsing experimental autoimmune encephalomyelitis (CREAE)

Abstract

Experimental autoimmune encephalomyelitis (EAE) is a T cell-mediated inflammatory and demyelinating disorder of the central nervous system. Depending on the experimental conditions, it takes an acute monophasic or a chronic relapsing-remitting course. We have previously reported that the incidence and severity of acute EAE in mice are reduced by administration of interferon (IFN)-γ and augmented by treatment with neutralizing antibodies against IFN-γ. Here, we investigated the role of IFN-γ in chronic relapsing models of EAE (CREAE) in SJL/J and Biozzi ABH mice. Spontaneous relapses in Biozzi mice as well as induced relapses in SJL/J mice were facilitated by administration of neutralizing monoclonal antibody (mAb) against IFN-γ in the disease-free interval. The enhancing effect of anti-IFN-γ mAb given before and during the primary attack did not carry over to the relapses. However, early administration of IFN-γ in Biozzi mice, which developed spontaneous relapses in a high proportion, provided partial protection not only against the first attack, but also against subsequent relapses. Administration of exogenous IFN-γ during the remission phase provided some protection against subsequent relapses. These results indicate that in both types of relapses, IFN-γ is produced and does provide a certain degree of protection against disease progression.