Aukrust P, Ueland T, Lien E, Bendtzen K, Müller F, Andreassen A K, Nordøy I, Aass H, Espevik T, Simonsen S, Frøland S S, Gullestad L
Medical Department A, University of Oslo, Rikshospitalet, Norway.
Am J Cardiol. 1999 Feb 1;83(3):376-82. doi: 10.1016/s0002-9149(98)00872-8.
Inflammatory cytokines may play a pathogenic role in the development of congestive heart failure (CHF). Elevated circulating levels of inflammatory cytokines have been reported in CHF, but most studies have focused on only a few cytokine parameters. However, the activity of these cytokines are modulated by soluble cytokine receptors and cytokines with anti-inflammatory activities, and in the present study several of these interacting factors were examined simultaneously in 38 CHF patients with various degrees of heart failure and in 21 healthy controls. Patients with CHF had increased plasma concentrations of tumor necrosis factor (TNF)alpha, interleukin-6, soluble TNF receptors and the soluble interleukin-6 receptor, glycoprotein (gp)130. They also had elevated ratios of TNFalpha/soluble TNF receptors and interleukin-6/soluble gp130 as well as enhanced interleukin-6 bioactivity in serum, suggesting inflammatory net effects. In addition to raised circulating levels of inflammatory cytokines, CHF patients with severe heart failure also had abnormalities in the levels of anti-inflammatory cytokines, with decreased levels of transforming growth factor beta1 and inadequately raised interleukin-10 in relation to the elevated TNFalpha concentrations. This dysbalance between inflammatory and anti-inflammatory cytokines was also found in monocyte supernatants from CHF patients. The abnormalities in the cytokine network were most pronounced in patients with the most severe heart failure, and several of the immunologic parameters, in particular soluble gp130, were correlated with variables reflecting deranged hemodynamic status. The present study analyzing the complexity of the cytokine network in CHF, demonstrates profound disturbances in the levels of both inflammatory and anti-inflammatory mediators with a marked dysbalance favoring inflammatory effects.
炎症细胞因子可能在充血性心力衰竭（CHF）的发生发展中起致病作用。已有报道CHF患者循环中炎症细胞因子水平升高，但大多数研究仅关注少数细胞因子参数。然而，这些细胞因子的活性受可溶性细胞因子受体和具有抗炎活性的细胞因子调节，在本研究中，同时检测了38例不同程度心力衰竭的CHF患者和21例健康对照者中几种相互作用的因子。CHF患者血浆中肿瘤坏死因子（TNF）α、白细胞介素-6、可溶性TNF受体、可溶性白细胞介素-6受体、糖蛋白（gp）130浓度升高。他们血清中TNFα/可溶性TNF受体和白细胞介素-6/可溶性gp130的比值也升高，且白细胞介素-6生物活性增强，提示存在炎症净效应。除了循环炎症细胞因子水平升高外，重度心力衰竭的CHF患者抗炎细胞因子水平也异常，转化生长因子β1水平降低，白细胞介素-10相对于升高的TNFα浓度升高不足。CHF患者单核细胞上清液中也发现了炎症和抗炎细胞因子之间的这种失衡。细胞因子网络异常在心力衰竭最严重的患者中最为明显，一些免疫参数，特别是可溶性gp130，与反映血流动力学紊乱状态的变量相关。本研究分析了CHF中细胞因子网络的复杂性，结果表明炎症和抗炎介质水平均存在严重紊乱，明显失衡，有利于炎症效应。
