STAPHYLOCOCCAL-ENTEROTOXIN-B AND TUMOR-NECROSIS FACTOR-ALPHA-INDUCED RELAPSES OF EXPERIMENTAL ALLERGIC ENCEPHALOMYELITIS - PROTECTION BY TRANSFORMING GROWTH-FACTOR-BETA AND INTERLEUKIN-10

A study was made of the ability of the superantigen staphylococcal ent erotoxin B (SEB) to induce relapses of experimental allergic encephalo myelitis (EAE) in SJL mice that had partially or completely recovered from acute EAE. We find that a single injection of 0.05 mg SEB i.v. in duces mild relapses in 50% of such mice. In addition, tumor necrosis f actor (TNF)-alpha (0.2 mu g, i.p.) also induces EAE relapses in 43% of SJL mice when injected 1-2 months after recovery. SEB does not induce a second relapse if reinjected when V beta 17a(+) T cells are still p artially deleted. In these mice, however, TNF-alpha is equally effecti ve in inducing relapses as in mice that did not receive SEB previously . We showed earlier that transforming growth factor (TGF)-beta and TNF -alpha have antagonistic effects on experimental autoimmune diseases; e.g., in spontaneously relapsing EAE, TGF-beta and anti-TNF were prote ctive, while anti-TGF-beta caused disease exacerbation. Interleukin (I L)-10 is also known to counteract certain TNF effects. We now find tha t both human IL-10 and TGF-beta 2 lower the incidence of EAE relapses when given simultaneously with SEB or TNF-alpha. The protective effect of TGF-beta is significant only against relapses induced by SEB (redu ced to 9%), and that of IL-10 only against relapses induced by TNF (re duced to O%) with the treatment regimens employed. Neutralizing anti-T GF-beta does not increase the incidence of SEB-induced EAE relapses. I n contrast, anti-IL-10 increases both the incidence and the severity o f such relapses. We conclude that TNF production is probably important in causing EAE relapses, but that other aspects of the SEB-induced re activation of myelin-specific T cells also contribute. Furthermore, en dogenous IL-10 rather than TGF-beta production appears to limit the su sceptibility to induction of EAE relapses in this model.