The influence of cyclosporin A on proteininduced uveitis in the rabbit

Until now immunosuppressive drugs have mainly been used to treat ocular diseases considered to have an autoimmune pathogenesis. The authors investigated whether cyclosporin A (CsA) could also prevent intraocular inflammation mediated by a foreign antigen. To this purpose, uveitis was induced by injection of human serum albumin (HSA) into the vitreous of rabbits. Subcutaneous injection of CsA prevented the induction of uveitis. Treatment of CsA had to be started at the time of intravitreal antigen injection and did not suppress the reaction when started at the onset of uveitis. Suppression of uveitis correlated with an inhibition of the antibody response against the injected HSA. Animals in which uveitis was suppressed by CsA did not develop a recurrent uveitis after intravenous challenge with the antigen, but did develop a primary inflammatory response after a repeated injection of HSA into the vitreous. The most likely interpretation of the findings presented in this paper are as follows. CsA blocks T helper cells through an inhibition of IL-2 gene activation. This in turn blocks release of other T helper cell cytokines which are essential for the activation of B lymphocytes into antibody producing plasma cells. These observations thus show that CsA can suppress both cell-mediated as well as antibody-mediated models of uveitis.