摘要
目的:研究甲氨蝶呤(m ethotrexate,MTX)对活动性类风湿关节炎(rheum atoid arthritis,RA)患者的疗效,探讨该药治疗类风湿关节炎的免疫学机制,了解MTX对RA患者血清中Th1/Th2型细胞因子的作用,为临床MTX治疗RA提供理论依据。方法:入选30例活动性RA患者,每周1次口服MTX(首次7.5 mg,每周递增2.5 mg至15 mg),疗程24周。采用美国风湿病学会(ACR)疗效评定标准,采用酶联免疫吸附双抗夹心法(ELISA)检测健康对照组以及RA患者MTX治疗前后血清中的细胞介素IL-1β,IL-6,IL-10,肿瘤坏死因子TNFα-和INFγ-浓度。结果:(1)MTX治疗第2周ACR20达到23%(7/30),至24周时ACR20上升至70%(21/30),ACR70也升至10%(3/30)。临床病情活动性指标(如晨僵、红细胞沉降率、压痛关节数、肿胀关节数、休息痛、患者及医生评价)较治疗前均有显著改善。(2)RA患者血清中的炎性细胞因子IL-6(46.83±35.81vs.20.92±17.98,P=0.028),TNFα-(162.52±107.63vs.18.32±14.36,P=0.001),INFγ-(67.79±43.76vs.35.78±27.51,P=0.004)等的水平均高于健康对照组,且差异具有统计学意义。抗炎性细胞因子IL-10的水平低于健康对照组(46.17±26.70vs.47.21±28.94),但差异无统计学意义(P=0.887)。(3)MTX治疗RA后血清中Th1型细胞因子与治疗前相比,IL-1β(7.47±7.33,P=0.265),IL-6(26.01±25.64,P=0.025),INFγ-(41.53±13.49,P=0.015),TNFα-(123.36±89.61,P=0.018)等水平均明显降低,而Th2型细胞因子IL-10的水平明显提高(71.76±41.01,P=0.02)。结论:MTX治疗活动性RA起效早,疗效显著。并且MTX可以下调RA患者血清中IL-1β,IL-6,TNFα-和INFγ-水平,同时上调IL-10水平,抑制了Th1型细胞因子的炎症作用,增强了Th2型细胞因子的效应,从而抑制或控制了RA的病情发展。
Objective： To examine the clinical benefit and impact on cytokine production by methotrexate in rheumatoid arthritis. Methods： Thirty patients with RA were treated with oral methotrexate （mean, 15 mg per week） as monotherapy for 24 weeks. Clinical assessment using the American College of Rheumatology （ACR） criteria for improvement was performed at baseline and at the end of 2, 4, 8, 12 and 24 weeks. The pro-inflammation cytokine TNF-α, INF-γ, IL-β , IL-6 and anti-inflammation cytokine IL-10 were measured in RA sera at baseline and after 24 weeks of therapy. Results： There was remarkable improvement in disease activity following the MTX treatment. At the end of 24 weeks, the percent age of ACR20 was 70% （21/30）, ACRS0 30% （9/30） and ACR70 10% （3/30）. The levels of IL-6（46. 83 ±35. 81vs. 20.92±17.98,P=0.001）, TNF-α （162. 52 ±107. 63 vs. 18.32±14.36,P= 0.026） and INF-γ （ 67.79 ±43.76 vs. 35.78 ± 27.51, P =0.004） were significantly higher than those of the health control at baseline, respectively. The levels of TNF-α （123.36 ± 89.61,P =0.018）, INF-γ（41.53 ±13.49,P =0.015） , IL-1β（7.47 ±7.33,P =0.026） , IL-6（26.01 ±25.64,P =0.025） were significantly decreased after treatment with methotrexate. In contrast, IL-10 was remarkably increased （71.76 ±41.01, P =0.02 ）. Conclusion ： Methotrexate is effective in patients with rheumatoid arthritis. It can suppress the symptoms and joint damage. In addition, methotrexate treatment decreases the levels of pro-inflammatory cytokine, and increases the level of anti-inflammatory cytokine.
出处
《北京大学学报（医学版）》
CAS
CSCD
北大核心
2006年第4期356-359,共4页
Journal of Peking University:Health Sciences
