Cyclosporine G and D in experimental autoimmune uveoretinitis in the rat

Two analogs of cyclosporine A (CsA), cyclosporine G (CsG) and cyclosporine D (CsD), were compared to CsA with regards to their effects on experimental autoimmune uveoretinitis (EAU) as well as their adverse effects on renal functions. When administered daily on days 0-14 after immunization with S-antigen, CsA was the most effective of all in inhibiting EAU followed by CsG: 20-30 mg/kg/day of CsG appeared to have the same effect as 5 mg/kg/day of CsA. The effect of CsD was the least. When administered from day 7 after immunization, CsA and CsG were also effective in inhibiting the development of EAU. As for the adverse side effects, CsA was the most nephrotoxic: the toxic changes were morphologically found with doses of CsA at 10 mg/kg/day or higher. CsG and CsD were not nephrotoxic even at 30 mg/kg/day. The effects of CsG on immune responses were very similar to those of CsA. Both agents exhibited selective inhibition on the cell-mediated immune responses to S-antigen, while having no effect on antibody production.