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.
Kawashima
H
H
Department of Ophthalmology, University of Tokyo School of Medicine, Japan.
Mochizuki
M
M
Okumura
A
A
Fujino
Y
Y
Tange
T
T
Horiuchi
D
D
Higashihara
E
E
Kaku
H
H
Inaba
G
G
D000818:Animals; D000917:Antibody Formation / Q000187:drug effects; D000941:Antigens / Q000276:immunology; D019393:Arrestin; D001327:Autoimmune Diseases / Q000188:drug therapy*; D016572:Cyclosporine; D003524:Cyclosporins / Q000009:adverse effects / Q000097:blood / Q000494:pharmacology*; D005136:Eye Proteins / Q000276:immunology; D007111:Immunity, Cellular / Q000187:drug effects; D007668:Kidney / Q000187:drug effects / Q000503:physiopathology; D007677:Kidney Function Tests; D008297:Male; D051381:Rats; D011917:Rats, Inbred Lew; D012173:Retinitis / Q000188:drug therapy* / Q000276:immunology; D012882:Skin Tests; D014605:Uveitis / Q000188:drug therapy* / Q000276:immunology
D000941:Antigens; D019393:Arrestin; D003524:Cyclosporins; D005136:Eye Proteins; C045571:cyclosporin G; D016572:Cyclosporine; C050026:cyclosporin D