IL-10 has a protective role in experimental autoimmune uveoretinitis

The role of IL-10 in the regulation of ocular autoimmune disease wasstudied in experimental autoimmune uveoretinitis (EAU) elicited in mice byimmunization with the retinal antigen interphotoreceptor retinoid bindingprotein. IL-10-deficient mice were susceptible to EAU, indicating thatpathogenesis can occur without presence of IL-10. Treatment of normal micewith IL-10 for 5 days after uveitogenic immunization ameliorated subsequentEAU scores, and down-regulated antigen-specific production of tumornecrosis factor-alpha and IFN- gamma. A concomitant treatment with IL-4further reduced disease, and resulted in emergence of antigen-specific IL-4and IL-10 production, as well as in enhancement of the IgG1 antibodyisotype. IL-4 by itself was not protective. Only IL-10, but not IL-4, wasable to inhibit the function of differentiated uveitogenic T cells inculture. Expression of mRNA for Th1 and Th2 cytokines in the eye during thecourse of EAU showed that while a Th1 pattern predominated early, IL-10mRNA expression coincided with down-regulation of the Th1 response andresolution of EAU. Systemic neutralization of IL-10 during the expressionphase of EAU resulted in elevated disease scores. Our results suggest thatendogenous IL-10 limits expression of EAU and may play a role in thenatural resolution of disease. The data further suggest that exogenousIL-10 may be useful in therapeutic control of autoimmune uveitis. WhileIL-10 by itself is sufficient to suppress Th1 effector development andfunction, a concomitant administration of IL-4 is required to shift theautoimmune response towards a non-pathogenic Th2 pathway.