2-Buten-4-olide (2-B4O) inhibits type II collagen-induced arthritis in Lewis rats

2-Buten-4-olide (2-B4O) is an endogenous substance which suppresses appetite and/or food intake. We studied its effect on type II collagen-induced arthritis (CIA) in Lewis rats, an animal model for human rheumatoid arthritis. Bovine type II collagen with incomplete Freund's adjuvant was injected intradermally into Lewis rats to induce CIA. 2-B4O (50 or 100 mg/kg) significantly inhibited the expression of the clinical symptoms when administered i.p. daily from day 1 to 21 after immunization. Furthermore, administration of 2-B4O daily from day 15 to 21 significantly reduced the severity of symptoms in established CIA. In addition, the progression of soft tissue swelling and articular bone erosions were suppressed by daily administration of 2-B4O. 2-B4O also significantly suppressed the delayed-type hypersensitivity (DTH) response to type II collagen at doses of 50 and 100 mg/kg. Finally 2-B4O significantly 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 effects on CIA through the suppression of immune responses to type II collagen.