Effects and mechanisms of Clematis mandshurica Maxim. as a dual inhibitor of proinflammatory cytokines on adjuvant arthritis in rats

Effect and mechanism of Clematis mandshurica Maxim. water extract (CMA), a dual inhibitor of interleukin-1 (IL-1) and tumor necrosis factor-α (TNF-α), on rat adjuvant arthritis (AA) were investigated. Complete Freund's adjuvant (CFA) was used to induce AA in rats. The extents of inflammation and treatment response were evaluated with regard to lymphocyte proliferation. Serial evaluation was carried out on days 1, 7, 14, 21 and 28 after creation of inflammation. The lymphocyte proliferation study revealed cellular immunosuppression during the early phase of the disease. Administration of CMA on the same day or 5 days prior to inflammatory insult into the joint significantly reduced the inflammation as compared to the untreated animals in a dose dependent manner. The administration of CMA (2, 5 and 10 mg/kg, subcutaneously (s.c.)) inhibited the inflammatory response and restored the weight of body and immune organs of AA rats. Synoviocytes proliferation of AA rats significantly increased, and the levels of TNF-α and IL-1 in supernatants of synoviocytes in AA rats were also elevated compared with the nonimmunized rats group. The administration of CMA (2, 5 and 10 mg/kg, s.c.) reduced the above changes significantly. In contrast to TNF-α and IL-1, IL-10 production and the level of its mRNA of synoviocytes in AA rats were apparently decreased. CMA (2, 5 and 10 mg/kg, s.c.) markedly increased IL-10 in synoviocytes at protein and transcription level. The results indicated that CMA had a beneficial effect on rats AA due to modulating inflammatory cytokines production of synoviocytes, which played a crucial role in pathogenesis of this disease.