Stumpf Christian, Seybold Katrin, Petzi Sebastian, Wasmeier Gerald, Raaz Dorette, Yilmaz Atilla, Anger Thomas, Daniel Werner G, Garlichs Christoph D
Department of Cardiology, University of Erlangen-Nuremberg, Erlangen, Germany.
Eur J Heart Fail. 2008 Aug;10(8):733-9. doi: 10.1016/j.ejheart.2008.06.007. Epub 2008 Jul 2.
Evidence has shown that pro-inflammatory cytokines, especially TNF-alpha, are involved in the inflammatory response in the remodelling process after myocardial infarction (MI). Although IL-10, an anti-inflammatory cytokine, has been shown to antagonize some of the deleterious effects of TNF-alpha, little is known about its role in post-MI left ventricular (LV) dysfunction. The aim of the present study was to investigate whether a therapy with rhIL-10 could be beneficial in an animal model of post-MI heart failure (HF). Rats with experimental MI were treated with rhIL-10 (75 microg/kg/d sc) starting directly after MI induction, and continuing for 4 weeks. Controls were untreated MI and sham-operated rats. Cardiac function was assessed by echocardiography and cardiac catheterization 4 weeks after MI induction. Membrane-bound and soluble fractions of TNF-alpha, IL-6 and IL-10, the ratio of TNF-alpha to IL-10, serum levels of MCP-1 as well as myocardial macrophage infiltration, were analyzed. Treatment with rhIL-10 significantly improved post-MI LV function (FS +127%;, dP/dt(max) +131%; LVEDP -36%). This effect was associated with a significant decrease in pro-inflammatory cytokine and chemokine levels (TNF-alpha, IL-6, MCP-1) and furthermore resulted in a reduced myocardial infiltration of macrophages.
有证据表明，促炎细胞因子，尤其是肿瘤坏死因子-α（TNF-α），参与了心肌梗死（MI）后重塑过程中的炎症反应。尽管抗炎细胞因子白细胞介素-10（IL-10）已被证明可拮抗TNF-α的一些有害作用，但关于其在MI后左心室（LV）功能障碍中的作用知之甚少。本研究的目的是调查重组人IL-10（rhIL-10）治疗在MI后心力衰竭（HF）动物模型中是否有益。实验性MI大鼠在MI诱导后立即开始用rhIL-10（75微克/千克/天，皮下注射）治疗，并持续4周。对照组为未治疗的MI大鼠和假手术大鼠。在MI诱导4周后，通过超声心动图和心导管检查评估心脏功能。分析了TNF-α、IL-6和IL-10的膜结合和可溶性部分、TNF-α与IL-10的比值、单核细胞趋化蛋白-1（MCP-1）的血清水平以及心肌巨噬细胞浸润情况。rhIL-10治疗显著改善了MI后的LV功能（左室短轴缩短率增加127%；最大dp/dt增加131%；左室舒张末期压力降低36%）。这种作用与促炎细胞因子和趋化因子水平（TNF-α、IL-6、MCP-1）的显著降低相关，并且还导致心肌巨噬细胞浸润减少。
