Chronic relapsing experimental autoimmune encephalomyelitis (CREAE) in mice: enhancement by monoclonal antibodies against interferon‐γ

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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.