青蒿治疗难治性类风湿关节炎患者的疗效及对TH17/Treg细胞因子的影响

目的：探讨青蒿治疗难治性类风湿关节炎（rheumatoid arthritis，RA）患者的疗效及是否可纠正Th17/Treg失衡及对细胞因子的影响。方法：病例来源于某院风湿免疫科，64例难治性RA患者纳入，17例难治性RA患者继续应用MTX为对照组，23例难治性RA患者应用青蒿为青蒿治疗组，24例难治性RA患者应用TNFi拮抗剂+MTX为阳性对照组。予观察3组第0，4，8，12周疗效，ELISA法检测患者血清细胞因子水平IL-10、IL-17和TNF-α表达情况；多参数流式细胞术检测各组患者外周血Treg和Th17细胞表达水平。结果：（1）青蒿治疗组和阳性对照组第8周起疗效比MTX对照组对比有统计学意义；阳性对照组第4周起比青蒿治疗组效果有统计学意义；（2）青蒿治疗组和阳性对照组患者第8周血清IL-10浓度显著高于MTX组；青蒿治疗组和阳性对照组患者血清IL-17浓度显著低于MTX组。此外，青蒿治疗组和阳性对照组患者TNF-α、ESR和CRP浓度显著低于MTX组；（3）流式细胞仪检测示青蒿治疗组和阳性对照组患者Treg细胞百分比显著高于MTX组；青蒿治疗组和阳性对照组患者血清Th17细胞百分比显著低于MTX组。结论：青蒿治疗难治性类风湿关节炎患者效果明显优于MTX，但效果较TNFi拮抗剂+MTX差，其抑制炎性因子的机制可能通过纠正RA患者的TH17/Treg失衡达到治疗目的。

Effect of artemisinin on Th17/Treg and cytokines in patients with refractory rheumatoid arthritis

OBJECTIVE To investigate the efficacy in the refractory rheumatoid arthritis patients treated by artemisinin and whether it could correct Th17/Treg imbalances and effects on cytokines.METHODS Totally 64 patients with refractory rheumatoid arthritis were included in the study,17 patients with refractory RA receiving MTX in control group,23 patients with refractory RA receiving artemisinin in treatment group,24 patients with refractory RA receiving TNFi antagonists + MTX in positive control group.Different parameters were observed after 0,4,8,12 weeks.Serum levels of cytokines IL-10,IL-17 and TNF alpha were detected by ELISA method,Treg and Th17 expression levels in peripheral blood were detected by multi-parameter flow cytometry.RESULTS Efficacy was significantly improved in treatment group and positive control group compared with MTX group 8 weeks later.Statistical significance was observed in the difference between positive control group and treatment group 4 weeks later.The serum IL-10 concentrations in treatment group and positive control group patients were significantly higher than that of MTX group 8 weeks later,and the serum IL-17 concentrations of treatment group and positive control group were significantly lower than that of MTX group.In addition,the TNF alpha and hsCRP concentrations of treatment group and positive control group were significantly lower than that of MTX group.Treg cell percentages in treatment group and positive control group patients were significantly higher than that of MTX group.The Th17 cell percentages of treatment group and positive control group were significantly lower than that of MTX group.CONCLUSION The effect of artemisinin is superior to that of MTX in patients with refractory rheumatoid arthritis,but inferior to that of TNFi antagonists + MTX.The mechanism of inhibiting inflammatory cytokines may be achieved through correcting TH17/Treg imbalance in RA patients.