¡¾Abstract¡¿ AIM: To determine the inhibitory effects of methotrexate (MTX) and tripterygium glycosides (TG) on chemokine CCL5 production in synoviocytes isolated from patients with rheumatoid arthritis (RA). METHODS: Synoviocytes, isolated from 13 RA patients and 7 patients with osteoarthritis (OA), were cultured and stimulated with or without lipopolysaccharide (LPS) in the presence or absence of different dosages of MTX or TG. CCL5 level in culture supernatants was measured by enzymeª²linked immunosorbent assay (ELISA). RESULTS: RA synoviocytes spontaneously produced a higher level of CCL5 than OA synoviocytes did(P<0.05). Both MTX and TG were found to significantly inhibit LPSª²induced CCL5 production in RA synoviocytes(both P<0.001), while no significant difference was found between the two (P>0.05). Moreover, the inhibitory effect of MTX appeared to be in a dosage dependent manner at the concentration ranging from 5-20 ¦Ìg/L, whereas, TG showed its inhibitory effect only when its concentration reached 40 ¦Ìg/L . Furthermore, the inhibitory effect of TG was found to be correlated with TGª²induced cell death. CONCLUSION: The increased production of CCL5 by RA synoviocytes indicates a role of CCL5 in the pathogenesis of RA, and the modifying roles of MTX and TG for the disease might exist through their antiª²CCL5 effect and the inhibitory effect of TG is associated with its cytotoxic action. ......