TIME-COURSE AND CELLULAR-LOCALIZATION OF INTERLEUKIN-10 MESSENGER-RNAAND PROTEIN EXPRESSION IN AUTOIMMUNE INFLAMMATION OF THE RAT CENTRAL-NERVOUS-SYSTEM

Experimental autoimmune encephalomyelitis of the Lewis rat is a T-cell -mediated autoimmune disease of the central nervous system characteriz ed by a self-limiting monophasic course. In this study, we analyzed th e expression of the anti-inflammatory cytokine interleukin (IL)-10 at the mRNA and protein level in experimental autoimmune encephalomyeliti s actively induced with the encephalitogenic 68-86 peptide of guinea p ig myelin basic protein. Semiquantitative reverse transcriptase-polyme rase chain reaction revealed that IL-10 mRNA expression peaked during the acute phase of the disease at days 11 and 13. IL-10 mRNA was synch ronously induced with mRNA for the proinflammatory cytokine interferon -gamma. Immunocytochemistry with a monoclonal antibody against rat IL- 10 showed that the peak of IL-10 mRNA was accompanied by an abundant e xpression of IL-10 protein during the acute stage of the disease. Both in situ hybridization and double labeling immunocytochemistry in comb ination with confocal microscopy identified T cells, macrophages/micro glia, and astrocytes as major cellular sources of IL-10 in vivo. The e arly peak of IL-10 production was unexpected in light of its well-docu mented anti-inflammatory properties. Additional studies are required t o determine whether endogenous IL-10 contributes to rapid clinical rem ission typical for Lewis rat experimental autoimmune encephalomyelitis or if it plays other, yet undefined, roles in central nervous system autoimmunity.