A comparison of the effectiveness of cyclosporine A, D, and G in the treatment of experimental autoimmune uveitis in rats.
Cyclosporine A (CsA), one compound in the family of cyclosporines, 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 when 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 micrograms CsG was placed intracamerally into only one eye. The in vitro comparison of these cyclosporines' 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 most 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 inflammatory disease.
D000818:Animals; D001327:Autoimmune Diseases / Q000188:drug therapy*; D003524:Cyclosporins / Q000627:therapeutic use*; D004353:Drug Evaluation, Preclinical; D051381:Rats; D011917:Rats, Inbred Lew; D013329:Structure-Activity Relationship; D014605:Uveitis / Q000188:drug therapy / Q000276:immunology*
D003524:Cyclosporins