Effects of bucillamine, a new anti-rheumatic drug, on the experimental autoimmune uveitis in rats.
The in vitro and in vivo effects of a new immunomodulating agent, bucillamine, on experimental autoimmune uveitis (EAU) was studied in the rat. The capacity of S-antigen-sensitized lymphocytes to proliferate in response to the antigen or to produce antigen-specific antibodies was significantly suppressed by bucillamine in culture in a dose-dependent manner. The inhibitory effect of bucillamine was significantly enhanced by adding cyclosporin A (CYA) in the culture. The in vivo effects of bucillamine alone or in combination with CYA were further examined in Lewis rats immunized with S-antigen. All untreated rats developed severe EAU 17 days after S-antigen immunization, while rats treated with either bucillamine (200 mg kg-1 day-1) or CYA (2 mg kg-1 day-1) demonstrated milder symptoms of EAU. A combination therapy with bucillamine (20 or 200 mg kg-1 day-1) and CYA (2 mg kg-1 day-1) exhibited much more significant suppression of EAU induction. Although the in vivo treatment with bucillamine or CYA had no effects on the T-cell populations of spleen cells, the combination therapy significantly decreased the CD4+ T-cell population. As for the immune responses to S-antigen in drug-treated rats, bucillamine suppressed the lymphocyte proliferation to S-antigen, which was further suppressed by combination therapy with CYA. The serum antibody levels specific to S-antigen were not affected by tested dose of bucillamine.
Sawa
K
K
Department of Ophthalmology, Kurume University School of Medicine, Japan.
Mochizuki
M
M
D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology / Q000627:therapeutic use*; D000917:Antibody Formation / Q000187:drug effects; D000941:Antigens / Q000276:immunology; D019393:Arrestin; D001327:Autoimmune Diseases / Q000517:prevention & control*; D002455:Cell Division / Q000187:drug effects; D002478:Cells, Cultured; D003208:Concanavalin A / Q000276:immunology; D003520:Cyclophosphamide / Q000494:pharmacology; D003545:Cysteine / Q000031:analogs & derivatives* / Q000494:pharmacology / Q000627:therapeutic use; D004357:Drug Synergism; D005136:Eye Proteins / Q000276:immunology; D007108:Immune Tolerance / Q000187:drug effects; D008297:Male; D051381:Rats; D011917:Rats, Inbred Lew; D013154:Spleen / Q000276:immunology; D014605:Uveitis / Q000517:prevention & control*
D000894:Anti-Inflammatory Agents, Non-Steroidal; D000941:Antigens; D019393:Arrestin; D005136:Eye Proteins; D003208:Concanavalin A; D003520:Cyclophosphamide; D003545:Cysteine; C026535:bucillamine