CHRONIC RELAPSING EXPERIMENTAL AUTOIMMUNE ENCEPHALOMYELITIS (CREAE) IN MICE - ENHANCEMENT BY MONOCLONAL-ANTIBODIES AGAINST INTERFERON-GAMMA

Experimental autoimmune encephalomyelitis (EAE) is a T cell-mediated i nflammatory 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 ad ministration of interferon (IFN)-gamma and augmented by treatment with neutralizing antibodies against IFN-gamma. Here, we investigated the role of IFN-gamma, in chronic relapsing models of EAE (CREAE) in SJL/J and Biozzi ABH mice. Spontaneous relapses in Biozzi mice as well as i nduced relapses in SJL/J mice were facilitated by administration of ne utralizing monoclonal antibody (mAb) against IFN-gamma in the disease- free interval. The enhancing effect of anti-TFN-gamma mAb given before and during the primary attack did not carry over to the relapses. How ever, early administration of IFN-gamma in Biozzi mice, which develope d spontaneous relapses in a high proportion, provided partial protecti on not only against the first attack, but also against subsequent rela pses. Administration of exogenous IFN-gamma during the remission phase provided some protection against subsequent relapses. These results i ndicate that in both types of relapses, IFN-gamma is produced and does provide a certain degree of protection against disease progression.