INHIBITION OF EXPERIMENTAL AUTOIMMUNE UVEORETINITIS BY MYCOPHENOLATE MOFETIL, AN INHIBITOR OF PURINE METABOLISM

Mycophenolate mofetil (MM), an inhibitor of purine metabolism, was found to effectively inhibit the development of experimental autoimmune uveoretinitis (EAU) induced by S-antigen (SAg) in Lewis rats. MM completely inhibited EAU development in the majority of rats when administered daily, on days 0-13, at a dose of 30 mg kg(-1) day(-1). The drug was less effective, however, when given on days 7-20: minimal disease inhibition was achieved with the drug at 30 mg kg(-1) day(-1), although at 60 mg kg(-1) day(-1) the drug inhibited EAU development in most treated rats during the period of its administration. MM also completely inhibited in most treated rats the development of EAU adoptively transferred by SAg-sensitized lymphocytes, thus depicting its capacity to inhibit the efferent limb of the immune response. Treatment with MM also suppressed the cellular and humoral immune responses against SAg, with a good correlation being observed between the inhibition of these responses and suppression of EAU in the different groups of rats. MM is currently being examined for its immunosuppressive effects in humans and the data recorded here thus suggest this compound may be useful in treatment of immune-mediated uveitic conditions. (C) 1995 Academic Press Limited