Gong Kaizheng, Zhang Zhengang, Sun Xiaonin, Zhang Xin, Li Aihua, Yan Junfeng, Luo Qiuping, Gao Yang, Feng Yiliang
Department of Cardiology, The First People's Hospital of Yangzhou, Yangzhou, China.
Am Heart J. 2006 Jan;151(1):62-8. doi: 10.1016/j.ahj.2005.02.040.
Inflammatory mediators play an important role in the pathogenesis of chronic heart failure (CHF). Methotrexate (MTX) is used in the treatment of inflammatory-mediated diseases (eg, rheumatoid arthritis) because it modulates the expression of numerous inflammatory cytokines. However, no studies have assessed the effects of MTX on plasma levels of inflammatory mediators in patients with CHF.
In a prospective, randomized, placebo-controlled, single-blind study, 71 patients receiving conventional treatment were randomly allocated to either MTX group (7.5 mg once a week, n = 35) or placebo group (n = 36) with a follow-up of 12 weeks. The effects of MTX on plasma cytokine expression, left ventricular ejection fraction, left ventricular end-diastolic dimension, New York Heart Association (NYHA) functional class, 6-minute walk test distance, and quality of life (QOL) were determined in patients with CHF.
Sixty-two patients completed the study. The circulating levels of inflammatory mediators in patients with CHF were markedly elevated compared with healthy controls (P < or = .002). Methotrexate (n = 30) reduced plasma levels of tumor necrosis factor alpha (-15.6%, P < .05), interleukin 6 (-21.8%, P < .01), monocyte chemoattractant protein-1 (-22.6%, P < .01), soluble intercellular adhesion molecule-1 (-19.2%, P < .05), and C-reactive protein (-27.2%, P < .01) compared with baseline. Furthermore, interleukin 10 (15.8 %, P < .05) and soluble IL-1 receptor antagonist (36.1%, P < .01) expression was increased, whereas improvements in NYHA classification, 6-minute walk test distance, and QOL were found compared with baseline. Monocyte chemoattractant protein-1 expression was lower and soluble IL-1 receptor antagonist expression higher in the MTX than placebo group (n = 32). Furthermore, the left ventricular ejection fraction, left ventricular end-diastolic dimension, and incidence of main adverse cardiac events between the 2 groups were similar.
These results suggest that the addition of MTX to conventional therapy for CHF has significant anti-inflammatory effects and improves NYHA functional class, 6-minute walk test distance, and QOL.
炎症介质在慢性心力衰竭（CHF）的发病机制中起重要作用。甲氨蝶呤（MTX）用于治疗炎症介导的疾病（如类风湿性关节炎），因为它可调节多种炎症细胞因子的表达。然而，尚无研究评估MTX对CHF患者血浆炎症介质水平的影响。
在一项前瞻性、随机、安慰剂对照、单盲研究中，将71例接受常规治疗的患者随机分为MTX组（每周一次7.5mg，n = 35）或安慰剂组（n = 36），随访12周。测定MTX对CHF患者血浆细胞因子表达、左心室射血分数、左心室舒张末期内径、纽约心脏协会（NYHA）功能分级、6分钟步行试验距离和生活质量（QOL）的影响。
62例患者完成了研究。与健康对照组相比，CHF患者炎症介质的循环水平显著升高（P≤0.002）。与基线相比，MTX（n = 30）使血浆肿瘤坏死因子α水平降低（-15.6%，P < 0.05）、白细胞介素6降低（-21.8%，P < 0.01）、单核细胞趋化蛋白-1降低（-22.6%，P < 0.01）、可溶性细胞间黏附分子-1降低（-19.2%，P < 0.05）以及C反应蛋白降低（-27.2%，P < 0.01）。此外，白细胞介素10表达增加（15.8%，P < 0.05），可溶性白细胞介素-1受体拮抗剂表达增加（-36.1%，P < 0.01），与基线相比，NYHA分级、6分钟步行试验距离和QOL均有所改善。MTX组的单核细胞趋化蛋白-1表达低于安慰剂组（n = 32），可溶性白细胞介素-1受体拮抗剂表达高于安慰剂组。此外两组间左心室射血分数、左心室舒张末期内径和主要不良心脏事件发生率相似。
这些结果表明，在CHF常规治疗中加用MTX具有显著的抗炎作用，并可改善NYHA功能分级、6分钟步行试验距离和QOL。
