Early administration of IL-12 suppresses EAE through induction of interferon-γ

Recent findings have shown that IL-12, a key inducer of Th1 cell development, is not required in the pathogenesis of experimental autoimmune encephalomyelitis (EAE) as severe CNS inflammatory demyelination can develop in the absence of IL-12 or IL-12 responsiveness. These data raised the possibility of an immunomodulatory action of IL-12 in this disease model. We show here that IL-12 suppresses MOG35-55-induced EAE in the C57BL/6 mouse when administered during the early induction phase of the disease. The inhibitory effect is interferon-gamma-(IFN-gamma)-dependent, as clearly shown by lack of suppression in IFN-gamma-deficient mice, and is also accompanied by inhibition of mRNA expression of the proinflammatory cytokine IL-17. (C) 2004 Elsevier B.V. All rights reserved.