A Comparison of the Effectiveness of Cyclosporine A, D, and G in the Treatmeat of Expertmental Autoimmune Uveiitis in Rats

Abstract

Cyclosprine A (CsA), one compound in the family of cyclosprines, has effectively modulated the course of S-antigen induced experimental autoimmune uveitis (EAU). Cyclosporines G (CsG) and D (CsD), related to CsA in structure, were evaluated in their ability to prevent or modulate EAU in Lewis rats. 10 mg/kg/day IM of CsA effectively prevented the expression of EAU hen therapy began on the day of immunization, while the same dosage of CsG prevented EAU in 81% of animals, and CsD only in 33%. Higher concentrations of CsG (40 mg/kg/day) did effectively block manifestations of the disease. Topical administration of CsG did not prevent the expression of disease but local protection was seen when the 500 ug CsG was placed intracamerally into only one eye. The in vitro comparison of these cyclosprines’ capacity to alter proliferation and IL-2 release of a rat T-cell line capable of inducing EAU showed marked differences. CsA appeared to be mst effective at abrogating these cellular functions at all concentrations tested, while CsD was least effective. CsG, however, approached the effectiveness of CsA. CsG is felt to be markedly less nephrotoxic than CsA, the secondary effect that is most commonly encountered, and could potentially be useful in the treatment of human intra-ocular inflamnatory disease.