Objective To observe the possible anti-inflammatory and anti-angiogenesis effects of iguratimodon human synovial fibroblast cell line MH7A derived from patients with rheumatoid arthritis (RA).Methods MH7A cells were stimulated with interleukin (IL)-1β and treated simult aneously or sequenti-ally with different concentrations of iguratimod and methotrexate (MTX).Release of vascular endothelial growth factor (VEGF), endostatin (ES) and tumour necrosis factor-α (TNF-α) was quantified by enzyme linked immunosorbent assay (ELISA).The statistics software SPSS 13.0 was used for statistical analyses.The experimental data were analyzed in terms of variance analysis and LSD test.In all cases, a P value lower than 0.05 was considered significant.Results The concentrations of VEGF, ES and TNF-α of the control group were (57±98) pg/ml, (924±39) pg/ml, (16.40±6.08) pg/ml respectively, while those of the experimental group were (1 155±177) pg/ml, (295±35) pg/ml and (36.90±3.54) pg/ml respectively.The differences of VEGF (t=9.092, P＜0.01) and ES (t=19.685, P＜0.01) between the control group and the experimental group was statistically significant.There was significant difference in the levels of TNF-α between the two groups (t=2.495, P＜0.05).VEGF of the iguratimod groups was (640±127) pg/ml in the iguratimod group (100 μmol/L), (787±172) pg/ml in the iguratimod group (25 μmol/L), and (776±99) pg/ml in the iguratimod group (6.25 μmol/L).VEGF of the MTX groups was (1 322±264) pg/ml in the MTX group (100 μmol/L), (1 071±63) pg/ml in the MTX group (25 μmol/L), and (863±70) pg/ml in the MTX group (6.25 μmol/L).All concentration of the iguratimod groups could effectively reduce the expression of VEGF in MH7A cells.Compared with the experimental group, the difference was statistically significant (100 μmol/L group: t=4.264, P＜0.01;25 μmol/L group: t=3.045, P＜0.01;6.25 μmol/L group: t =3.132, P ＜0.01).MTX (6.25 μ mol/L) could reduce the expression of VEGF in MH7A cells.Compared with the experimental group, the difference was statistically significant (t=2.415,P＜0.05).ES of the iguratimod groups was (979±30) pg/ml in the iguratimod group (100 μmol/L), (842±14)pg/ml in the iguratimod group (25 μmol/L), and (485 ±72) pg/ml in the iguratimod group (6.25 μmol/L).ES of the MTX group was (934±23) pg/ml in the MTX (100 μmol/L) group, (825±28) pg/ml in the MTX group (25 μmol/L), and (772 ±44) pg/ml in the MTX group (6.25 μmol/L).Both iguratimod and MTX groups effectively increased the expression of ES in MH7A cells.Compared with the experimental group, the difference was statistically significant (100 μmol/L group: t=21.387, P＜0.01;25 μmol/L group: t=17.122,P＜0.01;6.25 μmol/L group: t=5.929, P＜0.01).The expression of ES of the iguratimod group (100 μmol/L)and iguratimod group(25 μmol/L) was higher than that of the iguratimod group (6.25 μmol/L).The difference was statistical significant(100 μmol/L group: 6.25 μmol/L group was t=15.458,P＜0.01;100 μmol/L group: 6.25 μ mol/L group was t=11.193, P＜0.01).The expression of ES of the iguratimod group(6.25 μmol/L) was lower than that of the MTX group (6.25 μmol/L).The difference was statistically significant (t=9.001, P＜0.01).TNF-α was (4.73 ±1.15) pg/ml in the iguratimod group (100 μmol/L), (4.40±2.65) pg/ml in the iguratimod group (25 μmol/L), and (4.40±0.10) pg/ml in the iguratimod group (6.25 μmol/L).TNF-α of the MTX groups were (4.40±3.61) pg/ml in the MTX group (100 μ mol/L), (13.40±16.46) pg/ml in the MTX group (25 μmol/L),and (21.73±16.50) pg/ml of the MTX group (6.25 μmol/L).Both the iguratimod groups and the MTX group (100 μmol/L) effectively reduced the expression of TNF-α in MH7A cells.Compared with the experimental group, the difference was statistically significant(100 μmol/L group: t=3.914, P＜0.01;25 μ mol/Lgroup: t=3.955,P＜0.01;6.25 μ mol/L group: t=3.955, P＜0.01).Theexpression of TNF-α of the MTX groups (100 μ mol/L and 25 μmol/L) reduced significantly.Compared with the experimental group, the difference was statistically significant (100 μmol/L group: t=3.955, P＜0.01;25 μmol/L group: t=2.859, P＜0.05).The expression of TNF-αof the iguratimod group (6.25 μmol/L) was lower than that of the MTX group (6.25 μmol/L).The difference was statistical significant (t=2.359, P＜0.05).Conclusion Iguratimod presents strong anti-inflammatory and antiangiogenesis properties.This study provides insight into the possible molecular mechanisms of iguratimod and suggests that it can be a medication for the treatment of chronic inflammatory diseases like RA.

Objective To observe the effects of iguratimod ( IT) combined with methotrexate ( MTX) in patients with refractory rheumatoid arthritis ( rRA) . Methods Sixty patients with rRA were randomly divided into 2 groups ( n=30 each group) . The cases in treatment group received 50 mg.d-1 of iguratimod and 10 mg of MTX for 16 weeks. The cases in control group were treated by 10-15 mg of MTX. DAS28 was analyzed. Levels of VEGF and endostatin ( ES) were quantified. Results In the treatment group,after 16-week treatment,DAS28,levels of VEGF and ES were (3.0±1.2),(818.9±178.8) pg.mL-1, (337.8±132.6) ng.mL-1,and those in the control group were (5.7±1.9),(1000.2±245.9) pg.mL-1,(253.8±77.8) ng.mL-1,respectively. In the treatment group,DAS28 and VEGF after the treatment were significantly decreased as compared with those before the treatment ( P<0.01) . The decrement was more significant in the treatment group than in the control group ( P<0.01) . At the 16th week of treatment,ES was significantly increased as compared with that before the treatment ( P<0.01) , and there was a significant difference between the treatment group and the control group (P<0.01). Conclusion Iguratimod combined with MTX have a prominent effect on rRA with high safety. The efficacy of IT on RA might be related with decreasing VEGF release,increasing ES production and alleviating synovium angiogenesis.