Anti-arthritic and immunoregulatory effects of TI-31 on collagen-induced arthritis.
TI-31 (TEI-3096, 6-p-chlorobenzyl-5H-2,3,6,7-tetrahydro-5,7-dioxothiazolo[3,2-a]pyr imidine) reduced bovine type II collagen-induced arthritis (CIA) in rats in a time- and dose-dependent manner. Oral TI-31 treatment in doses of 10 and 50 mg/kg daily for 7 days prior to collagen immunization depressed the development of arthritis. However, it had no obvious effect on CIA when administered daily for a 7-day or 28-day period after the immunization. This compound was also ineffective against the established arthritis. On the contrary, cyclophosphamide, dexamethasone, or ibuprofen strongly protected the animals from the development of arthritis and/or cured the established arthritis by these dose regimens. Both humoral and delayed-type hypersensitivity skin responses to bovine type II collagen were decreased in rats treated with TI-31 daily for 7 days before the induction of arthritis. These results suggest that TI-31 depresses CIA by regulating the immune response to collagen through a mechanism different from that of anti-inflammatory drugs or immunosuppressants.
Teijin Institute for Bio-medical Research, Tokyo, Japan.
K
K
Komoriya
I
I
Nagata
K
K
Kunisawa
T
T
Takeshita
T
T
Naruchi
D000818:Animals; D000917:Antibody Formation / Q000187:drug effects; D001168:Arthritis / Q000188:drug therapy*; D001169:Arthritis, Experimental / Q000139:chemically induced / Q000188:drug therapy* / Q000276:immunology; D003094:Collagen; D004305:Dose-Response Relationship, Drug; D007111:Immunity, Cellular / Q000187:drug effects; D007074:Immunoglobulin G / Q000096:biosynthesis; D007166:Immunosuppressive Agents; D008297:Male; D051381:Rats; D011919:Rats, Inbred Strains; D013844:Thiazoles / Q000494:pharmacology* / Q000627:therapeutic use
D007074:Immunoglobulin G; D007166:Immunosuppressive Agents; D013844:Thiazoles; C038415:TEI 3096; D003094:Collagen