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 10mg/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 10mg/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 10mg/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.