2-BUTEN-4-OLIDE (2-B40) INHIBITS TYPE-II COLLAGEN-INDUCED ARTHRITIS IN LEWIS RATS

2-Buten-4-olide (2-B4O) is an endogenous substance which suppresses ap petite and/or food intake. We studied its effect on type II collagen-i nduced arthritis (CIA) in Lewis rats, an animal model for human rheuma toid arthritis. Bovine type II collagen with incomplete Freund's adjuv ant was injected intradermally into Lewis rats to induce CIA. 2-B4O (5 0 or 100 mg/kg) significantly inhibited the expression of the clinical symptoms when administered i.p. daily from day 1 to 21 after immuniza tion. Furthermore, administration of 2-B4O daily from day 15 to 21 sig nificantly reduced the severity of symptoms in established CIA. In add ition, the progression of soft tissue swelling and articular bone eros ions were suppressed by daily administration of 2-B4O. 2-B4O also sign ificantly suppressed the delayed-type hypersensitivity (DTH) response to type II collagen at doses of 50 and 100 mg/kg. Finally 2-B4O signif icantly inhibited the formation of anti-type II collagen antibody at a dose of 100 mg/kg, but not at 50 mg/kg. These results suggest that 2- B4O has the strong inhibitory effects and therapeutic usefulness effec ts on CIA through the suppression of immune responses to type II colla gen.