ANTIBODIES AGAINST IL-12 PREVENT SUPERANTIGEN-INDUCED AND SPONTANEOUSRELAPSES OF EXPERIMENTAL AUTOIMMUNE ENCEPHALOMYELITIS

Immunization of (PL/J x SJL/J)F-1 mice with myelin basic protein (MBP) induces relapsing experimental autoimmune encephalomyelitis (EAE), Re lapses occur 7 to 10 days after recovery from the initial paralysis. S taphylococcal enterotoxins (SE) A or B, administered after recovery fr om the initial paralysis, induce immediate relapses. IL-12 is involved in the induction of EAE, Here, we show that SEA and SEE induce IL-12 in splenocytes from (PL/J x SJL/J)FI mice in vitro and increase the le vel of IL-12 in the sera of mice treated with these superantigens. IL- 12 administration mimics SE in inducing spontaneous relapses and in en hancing the severity and frequency of spontaneous relapses. IL-12 neut ralization blocks SE-induced and subsequent relapses of EAE, and, when instituted after recovery from the initial attack, prevents spontaneo us relapse. This is the first report of prevention of relapses of EAE with anti-IL-12 Ab, an approach which may prove useful in the preventi on of exacerbations in multiple sclerosis.