IL-10 HAS A PROTECTIVE ROLE IN EXPERIMENTAL AUTOIMMUNE UVEORETINITIS

The role of IL-10 in the regulation of ocular autoimmune disease was s tudied in experimental autoimmune uveoretinitis (EAU) elicited in mice by immunization with the retinal antigen interphotoreceptor retinoid binding protein. IL-10-deficient mice were susceptible to EAU, indicat ing that pathogenesis can occur without presence of IL-10, Treatment o f normal mice with IL-10 for 5 days after uveitogenic immunization ame liorated subsequent EAU scores, and downregulated antigen-specific pro duction of tumor necrosis factor-alpha and IFN-gamma. A concomitant tr eatment with IL-4 further reduced disease, and resulted in emergence o f antigen-specific IL-4 and IL-10 production, as well as in enhancemen t of the IgG1 antibody isotype, IL-4 by itself was not protective. Onl y IL-10, but not IL-4, was able to inhibit the function of differentia ted uveitogenic T cells in culture. Expression of mRNA for T(h)1 and T (h)2 cytokines in the eye during the course of EAU showed that while a T(h)1 pattern predominated early, IL-10 mRNA expression coincided wit h down-regulation of the T(h)1 response and resolution of EAU, Systemi c neutralization of IL-10 during the expression phase of EAU resulted in elevated disease scores. Our results suggest that endogenous IL-10 limits expression of EAU and may play a role in the natural resolution of disease. The data further suggest that exogenous IL-10 may be usef ul in therapeutic control of autoimmune uveitis, While IL-10 by itself is sufficient to suppress T(h)1 effector development and function, a concomitant administration of IL-4 is required to shift the autoimmune response towards a non-pathogenic T(h)2 pathway.