中华皮肤科杂志 ›› 2017, Vol. 50 ›› Issue (9): 636-640.

• 论著 • 上一篇    下一篇

重组人Ⅱ型肿瘤坏死因子受体-抗体融合蛋白联合甲氨蝶呤治疗银屑病及其对白细胞介素17A和肿瘤坏死因子α的影响

仝云蕾1,陈铭2,龚瑜2,张玲玲1,于倩1,王瑶1,史玉玲2   

  1. 1. 同济大学附属第十人民医院皮肤科
    2. 同济大学附属第十人民医院
  • 收稿日期:2016-12-21 修回日期:2017-02-11 出版日期:2017-09-15 发布日期:2017-08-31
  • 通讯作者: 史玉玲 E-mail:shiyuling1973@tongji.edu.cn
  • 基金资助:
    IL-27对银屑病iNKT细胞和Th17细胞免疫调节和效应应答的研究;iNKT细胞通过抑制Th17细胞的分化调节银屑病的发生发展

Recombinant human tumor necrosis factor receptor type Ⅱ: IgG Fc fusion protein combined with methotrexate for the treatment of psoriasis and their effects on levels of interleukin-17A and tumor necrosis factor-α

  • Received:2016-12-21 Revised:2017-02-11 Online:2017-09-15 Published:2017-08-31
  • Contact: Yuling SHI E-mail:shiyuling1973@tongji.edu.cn

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摘要： 目的 探讨重组人Ⅱ型肿瘤坏死因子受体-抗体融合蛋白（rhTNFR：Fc，商品名益赛普）联合甲氨蝶呤对中重度斑块型银屑病患者血清和单个核细胞中白细胞介素（IL）17A和肿瘤坏死因子（TNF-α）的影响。方法 2014年8月至2016年2月同济大学附属第十人民医院皮肤科门诊收治的30例中重度斑块型银屑病患者，分为益赛普组（15例）和益赛普 + 甲氨蝶呤组（15例），疗程24周。采用酶联免疫吸附法（ELISA）和实时定量PCR法检测两组患者治疗前后血清和外周血单个核细胞的IL-17A和TNF-α的浓度和mRNA表达水平。结果 治疗前益赛普 + 甲氨蝶呤组和益赛普组患者，血清IL-17A，TNF-α水平以及外周血PBMC中IL-17A，TNF-α mRNA的表达均显著高于健康对照组（P < 0.05）；治疗后，益赛普 + 甲氨蝶呤组血清IL-17A、TNF-α浓度（142.67 ± 14.82，70.07 ± 25.02）及外周血PBMC中IL-17A、TNF-α mRNA表达（1.12 ± 0.33，2.50 ± 1.04）与益赛普组血清IL-17A、TNF-α浓度（163.54 ± 23.18，91.98 ± 14.62）及外周血PBMC中IL-17A、TNF-α mRNA的表达（1.56 ± 0.77，3.61 ± 2.14）比较显著下降（P < 0.05）。结论 益赛普联合甲氨喋呤治疗银屑病疗效优于单用益赛普治疗，联合治疗可以缩短治疗时间，提高疗效，其作用机制可能与下调IL-17A、TNF-α的表达量有关。

Abstract: Tong Yunlei, Chen Ming, Gong Yu, Zhang Lingling, Yu Qian, Wang Yao, Shi Yuling Department of Dermatology, Tenth People′s Hospital of Tongji University, Shanghai 200072, China （Tong YL, Gong Y, Zhang LL, Yu Q, Wang Y, Shi YL）; Department of Physical Examination, Tenth People′s Hospital of Tongji University, Shanghai 200072, China （Chen M） Corresponding author: Shi Yuling, Email: shiyuling1973@tongji.edu.cn 【Abstract】 Objective To evaluate the effect of recombinant human tumor necrosis factor receptor type Ⅱ: IgG Fc fusion protein （rhTNFR:Fc, trade name Etanercept） combined with methotrexate on levels of interleukin-17A （IL-17A） and tumor necrosis factor-α （TNF-α） in the serum and mononuclear cells of patients with moderate to severe plaque psoriasis. Methods A total of 30 patients with moderate to severe plaque psoriasis were enrolled from Department of Dermatology of Tenth People′s Hospital of Tongji University between August 2014 and February 2016, and then were randomly and equally divided into Etanercept group and Etanercept + methotrexate group. The treatment lasted 24 weeks. Fifteen healthy blood donors served as healthy control group. Enzyme-linked immunosorbent assay （ELISA） and real-time quantitative PCR were performed to measure the serum levels and mRNA of IL-17A and TNF-α, respectively, in the patients of the above two groups before and after the treatment. Results Before the treatment, the serum levels of IL-17A and TNF-α, as well as the mRNA of IL-17A and TNF-α in peripheral blood mononuclear cells （PBMCs）, were all significantly higher in all the patients than in the healthy controls （all P < 0.05）. After the treatment, compared with the Etanercept group, the Etanercept + methotrexate group showed significantly lower serum levels of IL-17A （142.67 ± 14.82 vs. 163.54 ± 23.18, P < 0.05） and TNF-α （70.07 ± 25.02 vs. 91.98 ± 14.62, P < 0.05）, as well as lower mRNA of IL-17A （1.12 ± 0.33 vs. 1.56 ± 0.77, P < 0.05） and TNF-α in PBMCs （2.50 ± 1.04 vs. 3.61 ± 2.14, P < 0.05）. Conclusion Etanercept combined with methotrexate is superior to Etanercept alone in the treatment of psoriasis, and can reduce treatment duration and improve therapeutic effect, likely by down-regulating the of IL-17A and TNF-α.