血清白细胞介素-6水平在强直性脊柱炎疾病活动性和英夫利昔单抗治疗中作用机制研究

目的 通过比较抗肿瘤坏死因子单克隆抗体英夫利昔单抗(infliximab)治疗强直性脊柱炎(AS)患者前后血清细胞因子谱变化,筛选出与英夫利昔单抗疗效相关的差异表达细胞因子白细胞介素(IL)-6,并进一步探讨IL-6水平与AS的疾病活动性以及英夫利昔单抗治疗AS的作用机制.方法 本研究以一项开放性Ⅱ期临床研究为基础,使用英夫利昔单抗0、2、6周静脉输注,剂量为5 mg/kg,在0、2、6及10周对患者的疾病活动性和疗效进行评估,同时留取血清.首先使用蛋白芯片技术检测AS患者英夫利昔单抗治疗前后11种血清细胞因子谱的变化,对差异表达的细胞因子IL-6进一步用酶联免疫吸附试验(ELISA)检测.结果 11种血清细胞因子结果显示:IL-6水平是英夫利昔单抗治疗后唯一显著下降的细胞因子;进一步用ELISA检测AS患者血清IL-6水平,结果与蛋白芯片检测结果相似.相关分析显示:基线时IL-6水平与夜间痛、红细胞沉降率(ESR)、C反应蛋白(CRP)显著相关(P<0.01).结论 血清IL-6水平与AS的疾病活动性相关,英夫利昔单抗可能部分通过抑制IL-6发挥其疗效,IL-6是AS发病机制中又一重要的细胞因子.

Changes of serum interleukin-6 level in ankylosing spondylitis during treatment with a loading regimen of infliximab

Objective To compare the changes of 11 cytokines in ankylosing spondylitis(AS)before and after treatment with a loading regimen of infliximab and to evaluate the potential AS related discriminating cytokines and explore their value in diseases activity evaluation and possible association with therapeutic response.Methods This was an open-labeled,phase Ⅱ clinical trial conducted in 2 medical centers.All AS patients were infused with infliximab at week 0,2,6.The dosage was 5 mg/kg.Disease activity parameters were assessed at week 0,2,6 and 10.Eleven serum cytokines were detected using protein chip technique,then,serum IL-6 level wag measured by sandwich enzyme-linked immunosorbent assay(ELISA).Results IL-6 was detected by EHSA.Compared with healthy controls.IL-6 level incregsed markediy in AS(P<0.01).After treated with infliximab,IL-6 level decreased at week 2(P<0.01)and maintained at low level until week 10.Baseline serum IL-6 level was positively associated with AS disease activity index(night pain scores、ESRand CRP)(P<0.01).Conclusion Serum IL-6 level is associated with AS disease activity and may become a useful parameter for monitoring the clinical response of infliximab in AS patients.IL-6 is an important cytokine involved in the pathogenesis of AS.