IL-10 SUPPRESSES EXPERIMENTAL AUTOIMMUNE NEURITIS AND DOWN-REGULATES T(H)1-TYPE IMMUNE-RESPONSES

Experimental autoimmune neuritis (EAN) is a CD4(+) T cell-mediated mon ophasic inflammatory disorder of the peripheral nervous system (PNS). Cellular mechanisms, including macrophage and T cell infiltration, and cytokines like IFN-gamma and TNF-alpha are intimately involved in the pathogenesis of EAN. Interleukin 10 (IL-10) is a T(H)2-type cytokine that suppresses monocyte and T(H)1 cell functions. We examined the eff ect of recombinant human IL-10 (rHuIL-10) in EAN. When administered fr om the start of immunization with bovine peripheral myelin emulsified in Freund's complete adjuvant, IL-10 effectively suppressed and shorte ned clinical EAN. Even when given after Day 12 post immunization (pi) after clinical EAN had been established, IL-10 also effectively suppre ssed the severity of EAN. Pheripheral nerve myelin antigen-reactive IF N-gamma-secreting T(H)1-like cells were decreased in lymph nodes from IL-10-treated compared to control EAN rats. PNS autoantigen-induced T cell proliferation and B cell responses were not affected. P2 protein- reactive IFN-gamma, TNF-alpha, IL-1 beta, and IL-6 mRNA-expressing lym ph node cells were also downregulated in IL-10-treated compared to con trol EAN rats at Day 14 and 26 pi, while P2-reactive IL-4 mRNA-express ing cells were upregulated throughout treatment. Also, in IL-10-treate d EAN rats, upregulated anti-Pa IgG1 and downregulated IgG2a were obse rved. Our results clearly show that rHuIL-10 can suppress clinical EAN , and this suppression is associated with downregulation of T(H)1 resp onses and macrophage function and upregulated T(H)2 responses. (C) 199 7 Academic Press.