Inflammatory Cytokines in Heart Failure: Mediators and Markers
Inflammatory Cytokines in Heart Failure: Mediators and Markers
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DOI：
10.1159/000338166
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发表时间：
2012-01-01
期刊：
影响因子：
1.9
通讯作者：
Aukrust, Pal
中科院分区：
文献类型：
--
作者：
Gullestad, Lars;Ueland, Thor;Aukrust, Pal
来自实验和临床试验的证据表明，炎症介质在慢性心力衰竭（HF）的发病机制中起重要作用，导致心脏重塑和外周血管紊乱。几项研究表明，HF患者血浆和循环白细胞以及衰竭心肌本身中的炎性细胞因子水平升高，如肿瘤坏死因子（TNF）α、白细胞介素（IL）-1 β和IL-6。有强有力的证据表明，这些介质参与导致心脏重塑的过程，如肥大、纤维化和凋亡。这些细胞因子中的一些也可以提供有用的预后信息，作为这种疾病的可靠生物标志物。一般来说，免疫调节治疗，除了少数例外，是中性的，甚至是有害的。然而，例如，抗TNF研究的阴性结果并不一定反对“细胞因子假说”。这些研究只是强调了开发治疗模式的挑战，这些治疗模式可以调节HF患者的细胞因子网络并产生有益的净效应。未来的研究应确定慢性HF免疫发病机制中的关键因素及其作用机制，特别是澄清这些分子的适应性和适应不良效应之间的平衡。这些研究是开发针对HF炎症和免疫病理机制的新治疗策略的先决条件。在这篇综述文章中，这些问题进行了深入的讨论，我们也认为，未来的治疗目标，如介质在先天免疫，趋化因子和介质在基质重塑的可能性。版权所有（C）2012 S. Karger AG，巴塞尔
Evidence from both experimental and clinical trials indicates that inflammatory mediators are of importance in the pathogenesis of chronic heart failure (HF) contributing to cardiac remodeling and peripheral vascular disturbances. Several studies have shown raised levels of inflammatory cytokines such as tumor necrosis factor (TNF)alpha, interleukin (IL)-1 beta and IL-6 in HF patients in plasma and circulating leukocytes, as well as in the failing myocardium itself. There is strong evidence that these mediators are involved in processes leading to cardiac remodeling such as hypertrophy, fibrosis and apoptosis. Some of these cytokines can also give useful prognostic information as reliable biomarkers in this disorder. In general, immunomodulating treatments have, with a few exceptions, been neutral or even harmful. However, the negative results of anti-TNF studies, for instance, do not necessarily argue against the 'cytokine hypothesis'. These studies just underscore the challenges in developing treatment modalities that can modulate the cytokine network in HF patients and result in beneficial net effects. Future studies should identify the crucial actors and their mechanisms of action in the immunopathogenesis of chronic HF and, in particular, clarify the balance between adaptive and maladaptive effects of these molecules. Such studies are a prerequisite for the development of new treatment strategies that target inflammatory and immunopathogenic mechanisms in HF. In this review article, these issues are thoroughly discussed, and we also argue for the possibility of future therapeutic targets such as mediators in innate immunity, chemokines and mediators in matrix remodeling. Copyright (C) 2012 S. Karger AG, Basel