Proinflammatory cytokine levels in patients with depressed left ventricular ejection fraction: A report from the studies of left ventricular dysfunction (SOLVD)
Proinflammatory cytokine levels in patients with depressed left ventricular ejection fraction: A report from the studies of left ventricular dysfunction (SOLVD)
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DOI：
10.1016/0735-1097(95)00589-7
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发表时间：
1996-04-01
影响因子：
24
通讯作者：
Mann, DL
中科院分区：
文献类型：
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作者：
TorreAmione, G;Kapadia, S;Mann, DL
目标。这项研究试图评估左心功能不全试验(SOLVD)患者的促炎细胞因子水平与他们在随机前的纽约心脏协会功能分级和神经激素状态的关系。在30%到40%的心力衰竭患者中发现肿瘤坏死因子-α水平升高。然而，目前尚不清楚心力衰竭患者亚群中是否存在肿瘤坏死因子-α。促炎症细胞因子表达增加的机制也不清楚。采用酶联免疫分析法检测SOLVD试验神经激素亚研究中随机选择的功能I~III级患者的血浆肿瘤坏死因子-α和白介素6水平；年龄匹配的健康受试者作为对照组。血浆水平。与年龄匹配的对照组(0.75+/-0.05pg/ml)相比，功能I~III级患者血清肿瘤坏死因子-α(p<；0.001)水平升高(分别为1.95+/-0.54，2.63+/-0.48，6.4+/-1.9pg/ml)，且随着患者功能状态的降低而逐渐升高。与年龄匹配的对照组(1.8+/-0.5pg/ml)相比，功能I~III级患者血浆白细胞介素6(p<；0.001)水平升高(分别为3.33±0.55、6.2+/-1.1、5.22±0.9pg/ml)，且随着患者功能状态的下降而逐渐升高。COX比例风险分析显示，血浆肿瘤坏死因子-α(p<；0.07)与生存期呈显著正相关，而血浆白介素6(p<；0.72)与生存期无显著相关。除心房利钠因子与循环肿瘤坏死因子-α水平呈弱相关(r=0.23，p=0.04)外，神经激素和促炎细胞因子水平之间无显著相关性。随着患者心力衰竭分级的恶化，患者循环中促炎症细胞因子水平升高。此外，神经体液轴的激活不太可能完全解释心力衰竭中促炎症细胞因子的作用。
Objectives. This study Sought to assess proinflammatory cytokine levels in patients in the studies of left ventricular dysfunction trial (SOLVD) in relation to both their New York Heart Association functional classification and their neurohormonal status before randomization.Background. Elevated levels of tumor necrosis factor-alpha have been identified in 30% to 40% of patients with heart failure. However, it is unclear wi;ich subsets of patients with heart failure elaborate tumor necrosis factor-alpha. It is also unclear what the mechanism for the increased expression of proinflammatory cytokines is.Methods. Tumor necrosis factor-alpha and interleukin-6 levels were analyzed by enzyme linked immunoassay using randomly selected plasma samples from patients in functional classes I to III who were enrolled in neurohormonal substudies of the SOLVD trial; age-matched healthy Subjects served as the control group.Results. Plasma levels. of tumor necrosis factor-alpha (p < 0.001) were elevated in patients in functional classes I to III ([mean +/- SD] 1.95 +/- 0.54, 2.63 +/- 0.48, 6.4 +/- 1.9 pg/ml, respectively) compared with age-matched control subjects (0.75 +/- 0.05 pg/ml) and were progressively elevated in relation to decreasing functional status of the patient. Plasma levels of interleukin-6 (p < 0.001) were elevated in patients in functional classes I to III (3.3 +/- 0.55, 6.2 +/- 1.1, 5.22 +/- 0.9 pg/ml, respectively) compared with age-matched control subjects (1.8 +/- 0.5 pg/ml) and were progressively elevated in relation to decreasing functional status of the patient. Cox proportional-hazards analysis showed that there was a trend toward significance between plasma tumor necrosis factor-alpha (p < 0.07) and survival, whereas there was no significant relation for plasma interleukin-6 (p < 0.72). Except for atrial natriuretic factor, which correlated weakly (r = 0.23, p = 0.04) with circulating tumor necrosis factor-alpha levels, there was no significant correlation between neurohormonal and proinflammatory cytokine levels.Conclusions. Circulating levels of proinflammatory cytokines increase in patients as their functional heart failure classification deteriorates. Moreover, activation of the neurohumoral axis is unlikely to completely explain the elaboration of proinflammatory cytokines in heart failure.