Suppression of Experimental Autoimmune Uveoretinitis by Anti-IL-17 Antibody

Abstract

Purpuse: To determine whether treatment with anti-IL-17 antibody could suppress the intraocular inflammation of experimental autoimmune uveoretinitis (EAU) in rats. Methods: Rats were immunized with interphotoreceptor retinoid binding protein (IRBP) R16 peptide and were treated with anti-IL-17 antibody. Clinical signs of inflammation and ocular histological sections were observed and graded. Cytokine levels of supernatants of cells from draining lymph nodes were measured by enzyme-linked immunosorbent assay (ELISA). Delayed-type hypersensitivity (DTH) and lymphocyte proliferation assay (LPA) were detected. Results: Treatment of EAU with anti-IL-17 antibody delayed the onset of ocular inflammation and markedly inhibited the development of EAU. Antigen-specific DTH and LPA were suppressed, whereas the level of interferon (IFN)-γ produced by draining lymph node cells was increased after treatment with anti-IL-17 antibody. There was no significant change of IL-5 level as compared with control rats. Conclusions: These findings demonstrate that blockade of endogenous IL-17 activity by treatment with anti-IL-17 antibody attenuates EAU in rats. IL-17 rather than IFN-γ plays a crucial role in the development of EAU, and that antagonism of IL-17 could be useful for the treatment of human intraocular autoimmune diseases.