Role of endogenous interleukin-12 (IL-12) in induced and spontaneous relapses of experimental autoimmune encephalomyelitis in mice.

Actively induced, chronic relapsing experimental autoimmune encephalomyelitis (CREAE) was studied in SJL/J and in Biozzi ABH mice. In Biozzi ABH mice, relapses occurred spontaneously with high frequency. In SJL/J mice, spontaneous relapses occurred infrequently; however they could be induced reproducibly by reimmunization. In both models, moderately increased levels of serum IL-12(p40) were consistently found shortly before primary attacks, but irregularly at later times. Injections of anti-IL-12 antibody inhibited disease development in both SJL/J and in Biozzi ABH mice. The time window during which treatment needed to be initiated in order to be effective, ranged from before induction until shortly before the symptoms of primary attacks emerged. Such treatment inhibited not only the first attack but also the spontaneous or induced relapses. Most significantly, anti-IL-12 antibody given during remission of primary disease inhibited actively re-induced relapses in SJL/J, but not spontaneous relapses in Biozzi ABH mice. These results indicate that endogenous IL-12 favours EAE development by crucially affecting the active induction process, but that a second burst of IL-12 production may not be necessary for triggering spontaneous relapses.