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-IJJ and TNF-a were significantly lower in the Ebosin-treated CIA rats compared with the untreated controls. In cultured fibroblast-like synoviocytes (FLS), remarkable suppression of IL-1P, TNF-a and IL-6 production was detected at both protein and mRNA levels after Ebosin administration. Ebosin also resulted in lower activities of IL-lp-converting enzyme and TNF-a-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 oflL-1P, TNF-a and IL-6 in the CIA rats.Reumatoid arthritis (RA) is an autoimmune disease which is characterized by persistent synovitis, systemic inflammation and autoantibodies. The synovial membrane is infiltrated by immune cells like macrophages and T cells, resulting in chronic production ofpro-inflammatory cytokines and matrix metalloproteinases (MMPs), leading to cartilage and bone degradation. The pro-inflammatory cytokines such as interleukin-l P (IL-l P), interleukin-6 (IL-6) and tumor necrosis factor-a (TNF-a) produced by innate immune cells play essential roles in pathogenesis of inflammatory arthritis (1-3). In the rat CIA, fibroblast-like synoviocytes (FLS) actively participate in the chronic inflammatory responses as a major cell population in the invasive pannus (4). FLS in the hyperplastic synovital lining layer express high levels of MMPs and angiogenic factors in response to several cytokines including IL-l Pand