IL-10 suppresses experimental autoimmune neuritis and down-regulates TH1-type immune responses.

Experimental autoimmune neuritis (EAN) is a CD4+ T cell-mediated monophasic 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 TH2-type cytokine that suppresses monocyte and TH1 cell functions. We examined the effect of recombinant human IL-10 (rHuIL-10) in EAN. When administered from the start of immunization with bovine peripheral myelin emulsified in Freund's complete adjuvant, IL-10 effectively suppressed and shortened clinical EAN. Even when given after Day 12 post immunization (pi) after clinical EAN had been established, IL-10 also effectively suppressed the severity of EAN. Pheripheral nerve myelin antigen-reactive IFN-gamma-secreting TH1-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 lymph node cells were also downregulated in IL-10-treated compared to control EAN rats at Day 14 and 26 pi, while P2-reactive IL-4 mRNA-expressing cells were upregulated throughout treatment. Also, in IL-10-treated EAN rats, upregulated anti-P2 IgG1 and downregulated IgG2a were observed. Our results clearly show that rHuIL-10 can suppress clinical EAN, and this suppression is associated with downregulation of TH1 responses and macrophage function and upregulated TH2 responses.