Exogenous IL-12 suppresses experimental autoimmune encephalomyelitis (EAE) by tuning IL-10 and IL-5 levels in an IFN-gamma-dependent way.

Endogenous IL-12 is considered to be required for the generation and function of pathogenic Th1 effector cells in experimental autoimmune encephalomyelitis (EAE). We show here that IL-12 administration together with the immunization suppressed actively induced CREAE in SJL/J and in Biozzi/ABH mice and even subsequent spontaneous relapse incidence and severity in Biozzi ABH mice. IL-12 given during remission of primary disease inhibited re-induced relapses in SJL/J, but not spontaneous relapses in Biozzi mice. The protective effect of IL-12 is time- and dose-dependent. Protection is accompanied by subsequent increased production of IL-10 and IL-5 by lymph node and spleen cells and an inhibition of cell proliferation. Mice depleted of IFN-gamma by administration of neutralizing antibodies were poorly protected by exogenous IL-12, indicating that the inhibitory effect of IL-12 is partially IFN-gamma dependent.