甲氨蝶呤对中重度斑块型银屑病患者T细胞相关细胞因子表达水平的影响

 目的:探讨甲氨蝶呤（MTX）治疗中重度斑块型银屑病16周后,应答组和未应答组外周血T细胞相关细胞因子IFN-γ、IL-4、IL-17a、IL-21及TGF-β表达水平的变化。方法：纳入采用MTX系统性治疗16周后的中重度斑块型银屑病患者作为研究对象,其中应答组49例、未应答组13例、健康对照组35例,分析并比较62例银屑病患者治疗前后、应答组和未应答组治疗后生化指标及外周血IFN-γ、IL-4、IL-17a、IL-21、TGF-β表达水平的差异,采用Pearson相关分析银屑病患者治疗前PASI评分与血清IFN-γ、IL-4、IL-17a、IL-21、TGF-β表达水平的相关性。结果:银屑病患者治疗16周后血清肌酐、尿酸、尿素氮、ALT及AST较治疗前明显升高（P值均＜0.05）,而应答组与未应答组所有生化指标相比较无明显差异。应答组治疗后血清IFN-γ［（749.03±76.77) pg/mL vs (953.69±101.58） pg/mL］、IL-17a［（756.96±101.73) pg/mL vs (963.75±64.38) pg/mL］、IL-21［（514.76±53.48) pg/mL vs (693.45±87.91) pg/mL］较治疗前明显降低（P值均＜0.05）,TGF-β［（433.59±65.39) pg/mL vs (298.36±77.83) pg/mL］较治疗前明显升高（P＜0.05）,而IL-4［（218.72±67.39) pg/mL vs (198.78±47.71) pg/ mL］较治疗前无明显差异;未应答组治疗前后所有细胞因子相比较均无明显差异（P值均＞0.05）。Pearson相关分析结果显示,治疗前患者PASI评分与IFN-γ、IL-17a、IL-21、TGF-β水平均存在明显相关（r值分别为0.25、0.75、0.66、-0.11,P值均＜0.05)。结论:MTX治疗银屑病的潜在机制可能与改善Th1/Th2、Th17/Treg细胞免疫失衡有关。

Influence of Methotrexate on circulatory levels of T lymphocyte related cytokines in patients with moderate to severe plaque psoriasis

Objective：To explore the changes in expression levels of T cell related cytokines, including IFN-γ, IL-4, IL-17a, IL-21 and TGF-β, in peripheral blood of responders and non responders after 16 weeks of Methotrexate (MTX) treatment. Methods: A total of 49 responders, 13 non responders and 35 healthy controls were enrolled in this study. Pearson analysis was used to determine the correlation between PASI scores and serum IFN-γ, IL-4, IL-17a, IL-21 and TGF-β levels in psoriatic patients before the treatment. Following the treatment, biochemical markers and serum levels of IFN-γ, IL-4, IL-17a, IL-21, and TGF-β were compared among responders, non responders and normal controls. Results: After 16 week treatment, psoriatic patients displayed significantly higher serum levels of creatinine, uric acid, urea nitrogen, ALT and AST (P<0.05 for all vs. pretreatment). Treatment with MTX markedly lowered serum levels of IFN-γ［(749.03±76.77) pg/mL vs. (953.69±101.58) pg/mL］, IL-17a［(756.96±101.73) pg/mL vs. (963.75±64.38) pg/mL］, and IL-21［(514.76±53.48) pg/mL vs. (693.45±87.91) pg/mL］(P<0.05 for all vs. pretreatment), while increasing TGF-β［(433.59±65.39) pg/mL vs. (298.36±77.83) pg/mL, P<0.05］ in the responder group. However, the serum levels of IL 4 did not change significantly ［(218.72±67.39) pg/mL vs. (198.78±47.71) pg/mL］. In contrast, MTX treatment did not significantly alter serum levels of cytokines in the non responder group (all P＞0.05). Prior to the treatment, PASI scores correlated with IFN-γ, IL-17a, IL-21 and TGF-β, with coefficient of 0.25, 0.75, 0.66, -0.11, respectively (P<0.05 for all). Conclusion: The potential mechanism of MTX in alleviating psoriasis may be via the improvement of the balance of Th1/Th2 and Th17/Treg.