肿瘤坏死因子拮抗剂对强直性脊柱炎患者血清相关细胞因子变化的影响及其机制研究

目的:观察肿瘤坏死因子(TNF)拮抗剂对强直性脊柱炎(AS)患者血清中IL-6、IL-17、IL-21、IL-23、TNF-α、TGF-β1表达的影响,结合临床指标的变化探讨肿瘤坏死因子拮抗剂治疗AS的机制与疗效。方法:治疗组应用益赛普联合西乐葆,益赛普25 mg,皮下注射,连用8周,治疗前后评估晨僵VAS评分、腰背痛VAS评分、Bath强直性脊柱炎功能指数(BASFI)及血沉等指标,记录不良反应。用酶联免疫吸附法检测25例肿瘤坏死因子拮抗剂联合COX-2抑制剂治疗前、治疗第4周和治疗8周后AS患者血清中IL-6、IL-17、IL-21、IL-23、TNF-α、TGF-β1的表达情况,检测对照组(20例单独应用COX-2抑制剂的AS患者)治疗前、治疗后的细胞因子水平。结果:肿瘤坏死因子拮抗剂组患者血清中IL-6、IL-17、IL-23、TNF-α的表达在治疗第4周和治疗8周后较本组治疗前及对照组均有明显下降(P0.05);细胞因子IL-21、TGF-β1的表达水平较本组治疗前及对照组无明显降低(P0.05);对照组患者血清中IL-6、IL-17、IL-21、IL-23、TNF-α、TGF-β1的表达在治疗后较治疗前均无明显下降(P0.05);治疗组应用肿瘤坏死因子拮抗剂后较治疗前晨僵及腰背痛VAS评分、BASFI、血沉均显著改善(P0.05),临床疗效优良率为88.0%,对照组优良率为50.0%,有显著差异(P0.05),且治疗组不良反应轻微。结论:肿瘤坏死因子拮抗剂可能是通过降低AS患者血清中一系列细胞因子的表达水平,改善患者的免疫功能及临床症状,延缓了病程进展。但由于病例较少,肿瘤坏死因子拮抗剂联合COX-2抑制剂治疗AS患者的疗效需要在临床中进一步观察。

Efects of the Tumor necrosis Factor Antagonists on the Expressions of SerumCytokines in Patients with Ankylosing Spondylitis and Research on the Mechanismof TNF

Objective:To observe the influence of Tumor Necrosis Factor (TNF) antagonist on the expression levels of IL-6, IL-17, IL-21, IL-23, TNF-Alpha and TGF-beta1 in blood serum of patients with ankylosing spondylitis (AS), and to investigate the mechanism and efficacy of TNF antagonist on treatment of AS on the basis of clinical data.Methods:The treatment group were given the etanercept combined with celebrex, etanercept was 25 mg by subcutaneous for 8 weeks, then the morning stiffness VAS score, back pain VAS score, bath Ankylosing Spondylitis Functional Index (BASFI) were assessed and the adverse reactions were recorded. The IL-6, IL-17, IL-21, IL-23, TNF-alpha and TGF-beta1 expression in serum of 25 cases with AS who were treated by the TNF antagonist combined with COX-2 inhibitors were detected by enzyme-linked immunosorbent assay before and after the treatment for 4 and 8 weeks. And the cytokine levels another 20 patients who were only given the COX-2 inhibitors were also detected before and after treatment.Results:The IL-6, IL-17, IL-23 and TNF-alpha expression in serumof TNF antagonist group and the control group obviously decreased after the treatment for 4 and 8 weeks than before (P<0.05); IL-21 and TGF-beta1 expression of patients in the treatment group had no significant decreased (P>0.05); IL-6, IL-17, IL-21, IL-23, TNF-alpha and TGF-beta1 in serum of control group had no significant decreased (P>0.05); The morning stiffness VAS score, back pain VAS score, BASFI and erythrocyte sedimentation rate obviously improved, the excellent clinical rate was 88.0%, while the control group was 50.0%, which had obviously significance (P<0.05), and the adverse reaction of treatment group was mild.Conclusion:TNF antagonist could decrease the cytokine expression levels of AS patients, improve the immune function and clinical symptoms, delay the disease progression. However, the efficacy of TNF antagonist combined with COX-2 inhibitors in treatment of AS patients should be further observed.