Chronic relapsing experimental autoimmune encephalomyelitis (CREAE) in mice: enhancement by monoclonal antibodies against interferon-gamma.
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)-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 induced relapses in SJL/J mice were facilitated by administration of neutralizing monoclonal antibody (mAb) against IFN-gamma in the disease-free interval. The enhancing effect of anti-IFN-gamma mAb given before and during the primary attack did not carry over to the relapses. However, early administration of IFN-gamma 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-gamma during the remission phase provided some protection against subsequent relapses. These results indicate that in both types of relapses, IFN-gamma is produced and does provide a certain degree of protection against disease progression.
Laboratory of Immunobiology, Rega Institute, University of Leuven, Medical School, Belgium.
H
H
Heremans
C
C
Dillen
M
M
Groenen
E
E
Martens
A
A
Billiau
D000818:Animals; D000911:Antibodies, Monoclonal; D002908:Chronic Disease; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000276:immunology*; D005260:Female; D007158:Immunologic Techniques; D007371:Interferon-gamma / Q000502:physiology*; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains
D000911:Antibodies, Monoclonal; D007371:Interferon-gamma