TNF blockade aggravates experimental chronic Chagas disease cardiomyopathy
TNF blockade aggravates experimental chronic Chagas disease cardiomyopathy
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DOI：
10.1016/j.micinf.2007.05.014
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发表时间：
2007-07-01
影响因子：
5.8
通讯作者：
Cunha-Neto, Edecio
中科院分区：
文献类型：
--
作者：
Bilate, Angelina M. B.;Salemi, Vera M.;Cunha-Neto, Edecio
慢性恰加斯病心肌病(CCC)由锥虫引起，是一种炎症性扩张性早期肌病，与循环中肿瘤坏死因子-α水平升高有关。我们研究了在弓形虫感染的慢性期用依那西普阻断肿瘤坏死因子是否可以抑制实验性CCC的发展。观察依那西普对大鼠存活率、寄生率、左心功能、心肌炎程度、纤维化程度、左室心肌细胞因子和肿瘤坏死因子-α诱导基因表达的影响。与感染的未经治疗的动物相比，接受治疗的动物的左心功能显著降低。依那西普治疗不改变血液和心脏寄生率及存活率。在接受治疗的动物中，炎症浸润物主要位于心内膜下区域，而在未接受治疗的动物中，炎症分散在整个心肌中。治疗组大鼠左室心肌IL-10基因表达显著高于未治疗组，iNOS表达显著低于未治疗组。两组肿瘤坏死因子-α、干扰素-γ、转化生长因子-β、A20和心钠素的mRNA表达相似。我们的结果提示，用依那西普阻断肿瘤坏死因子-α/肿瘤坏死因子-α可增强克氏锥虫所致慢性心肌病患者的左心功能不全，而肿瘤坏死因子信号的缺失可能对查加斯病心肌病患者的衰竭心脏有害。(C)2007年爱思唯尔·马森公司。版权所有。
Chronic Chagas disease cardiomyopathy (CCC), caused by Trypanosonra cruzi, is an inflammatory dilated eardiomyopathy associated with increased circulating levels of TNF-alpha. We investigate whether TNF blockade with Etanercept during the chronic phase of T. cruzi infection could attenuate experimental CCC development. The effect of Etanercept was evaluated after 11 months of T. cruzi infection on survival, parasitism, left ventricular function, intensity of myocarditis, fibrosis, and left ventricular mRNA expression of cytokines and TNF-alpha-induced genes. Left ventricular function was significantly reduced in treated animals as compared to infected untreated animals. Blood and cardiac parasitism as well as survival rate were not altered with Etanercept treatment. Inflammatory infiltrates were located predominantly in the subendocardic region in treated animals, whereas in untreated animals inflammation was scattered throughout the myocardium. Left ventricular mRNA IL-10 expression was significantly higher, and iNOS, significantly lower in treated than in untreated animals. mRNA expression of TNF-alpha, IFN-gamma, TGF-beta, A20 and ANP was similar in both groups. Our results suggest that TNF-alpha/LT-alpha blockade with Etanercept enhances left ventricular dysfunction in T. cruzi-induced chronic cardiomyopathy and the absence of TNF signaling may be deleterious to the failing heart in Chagas disease cardiomyopathy. (C) 2007 Elsevier Masson SAS. All rights reserved.