Objective: To study the therapeutic effects and possible mechanism of tripterginum wilfordii polyglycoside (TWP) combined with leflunomide (LEF) on rat adjuvant arthritis (AA). Method: The murine collagen-induced arthritis model was established

then the arthritic rats were divided into control group

AA model group

LEF group

TWP group and TWP+LEF group; after treatment

the rats paw edema and arthritis index (AI) were evaluated; the levels of serum interleukin(IL)-1β

IL-6 and tumor necrosis factor alpha(TNF-α) were detected by radioimmunoassay method

serum interferon-gamma(IFN-γ)

IL-4 and prostaglandin E2(PGE2) by ELISA

and serum matrix metalloproteinases(MMP)-9 and MMP-2 by gelatin zymography assay. Result: ① Compared with AA model group

the hind paw swelling and AI in LEF group

TWP group and TWP+LEF group were significantly decreased (P<0.01)

especially in TWP+LEF group (P<0.05). ② The levels of serum IL-1β

TNF-α

IL-6

and PGE2 were notably higher in AA model group than control group (all P<0.01)

which was significantly decreased in three treatment groups (P<0.01 or P<0.05)

and their serum concentration was lower in TWP+LEF group than both LEF and TWP group (P<0.01 or P<0.05). ③ Compared with control group

the increase of serum IFN-γ and decrease of serum IL-4 was observed in model group (P<0.01). But the significant down-graduated expression of IFN-γ and up-graduated expression of IL-4 were found after treatment

particularly in TWP+LEF group (P<0.01). Conclusion: The combined use of TWP and LEF can significantly relieve the arthritis syndrome in AA rats by reducing the expression of serum cytokines

as well as inhibiting joint damage

and its therapeutic effect is better than used separately.