ANTI-INFLAMMATORY EFFECT OF EBOSIN ON RAT COLLAGEN-INDUCED ARTHRITIS THROUGH SUPPRESSING PRODUCTION OF INTERLEUKIN-1 beta, INTERLEUKIN-6 AND TUMOR NECROSIS FACTOR-alpha

Reumatoid arthritis (RA) is an autoimmune disease which has been studied experimentally using a wide variety of animal models including collagen-induced arthritis (CIA). Using this CIA model we studied the therapeutic effects and mechanism of action of Ebosin, a novel exopolysaccharide produced by Streptomyces sp. 139, on arthritis. Ebosin at 200, 400 and 600 mg/kg/day was orally administered to rats respectively between day 10 and 30 after immunization with chicken type II collagen. With the treatment arthritic progression was remarkably suppressed. Levels of anti-type II collagen specific antibody, IL-1 beta and TNF-alpha were significantly lower in the Ebosin-treated CIA rats compared with the untreated controls. In cultured fibroblast-like synoviocytes (FLS), remarkable suppression of TNF-alpha and IL-6 production was detected at both protein and mRNA levels after Ebosin administration. Ebosin also resulted in lower activities of IL-1 beta-converting enzyme and TNF-alpha-converting enzyme in FLS. Based on these results, it is concluded that development and progression of rat CIA can be significantly suppressed by orally-administrated Ebosin. The therapeutic effect may be attributed to its inhibition in the production of IL-1 beta, TNF-alpha and IL-6 in the CIA rats.