This study examined the inhibitory effect of triptolid(TP)on tumor necrosis factor-α(TNF-α)secreted from peripheral blood monocular cells(PBMCs)and the association of the inhibitory effect with TNF-α-308 gene polymorphisms in rheumatoid arthritis(RA)patients.Gene polymorphism at A-G site 308 in the promoter region of TNF-α gene was detected in 42 RA patients by using allele specific polymerase chain reaction(AS-PCR)assay.PBMCs were harvested from these patients and treated first with lipopolysaccharides(LPS)and then with different doses of TP(1,5.4 and 15 ng/mL).The TNF-α level in the supeatants was measured by enzyme-linked immunosorbent assay(ELISA).The results showed that TNF-αlevel in the supeatants of TP(1 ng/mL)-treated PBMCs was decreased by 3.80% and 4.91%,respectively,in the patients with AA and AG genotypes,when compared with those treated with LPS alone(P > 0.05).Moreover,the TNF-α level in the patients with GG genotype was reduced by 20.74%(P < 0.05).When PBMCs were treated with TP at 5.4 ng/mL,TNF-α levels in the patients with AA,AG,and GG genotypes were decreased by 20.42%,34.73%,and 41.69%,respectively(P 0.05).It was concluded that gene polymorphism at TNF-α-308 sites may relate to the secretion of TNF-α in RA patients.TP has different inhibitory effects on the secretion of TNF-α in the patients harboring different genotypes,which may be one of the reasons for individual variation in response to TP.