慢性心力衰竭患者循环肿瘤坏死因子-α水平：与其可溶性受体II、白细胞介素-6及神经体液变量的关系

Circulating tumor necrosis factor-alpha levels in chronic heart failure: relation to its soluble receptor II, interleukin-6, and neurohumoral variables.

作者信息

Koller-Strametz J, Pacher R, Frey B, Kos T, Woloszczuk W, Stanek B

机构信息

Department of Cardiology, University of Vienna, Austria.

出版信息

J Heart Lung Transplant. 1998 Apr;17(4):356-62.

PMID:9588580

Abstract

The cytokines tumor necrosis factor-alpha (TNF-alpha) and interleukin-6 (IL-6) are increased in the circulation of patients with chronic heart failure. However, their correlation with left ventricular dysfunction has not yet been thoroughly evaluated, and their interrelation with other neurohumoral systems, such as the adrenergic system and endothelin, is unclear. Therefore TNF-alpha, its soluble receptor II, IL-6, big endothelin, and noradrenaline levels were simultaneously measured in venous blood from 65 patients with heart failure in New York Heart Association (NYHA) class II to IV during therapy with digitalis, furosemide, and enalapril. TNF-alpha plasma levels were 3.2+/-0.2 SEM pg/ml in 38 patients in NYHA function class II, 4.0+/-0.3 SEM pg/ml in 16 patients in NYHA function class III, and 5.3+/-0.9 SEM pg/ml in 11 patients in NYHA function class IV (p < 0.001 vs NYHA function class II). IL-6 plasma levels were 3.1+/-0.6 SEM pg/ml in 38 patients in NYHA function class II, 5.2+/-0.8 SEM pg/ml in 16 patients in NYHA function class III, and 13.3+/-3.9 SEM pg/ml in 11 patients in NYHA function class IV (p < 0.0001 vs NYHA function class II andp < 0.0001 vs NYHA class III). Thus both cytokines increased with increasing severity of heart failure, but only IL-6 plasma levels were different in patients in the more severe function classes. TNF-alpha correlated closely with TNF soluble receptor II (r = 0.8, p < 0.0001) and modestly with serum creatinine (r = 0.6, p < 0.0001), whereas IL-6 plasma levels were not statistically related to kidney function. Significant modest correlations were also found among TNF-alpha and IL-6 (r = 0.3, p < 0.01), big endothelin (r = 0.3, p < 0.01), and noradrenaline levels (r = 0.4, <0.001). This study supports the hypothesis that in heart failure both cytokines, TNF-alpha, and IL-6, as well as neurohumoral factors, play a role in the clinical progression of the disease. Thereby levels of TNF-alpha but not IL-6 seem to be related to concomitant kidney dysfunction.

摘要

细胞因子肿瘤坏死因子-α（TNF-α）和白细胞介素-6（IL-6）在慢性心力衰竭患者的循环系统中水平升高。然而，它们与左心室功能障碍的相关性尚未得到充分评估，并且它们与其他神经体液系统（如肾上腺素能系统和内皮素）的相互关系也不清楚。因此，在65例纽约心脏协会（NYHA）心功能II至IV级的心力衰竭患者接受洋地黄、呋塞米和依那普利治疗期间，同时测定了他们静脉血中的TNF-α、其可溶性受体II、IL-6、大内皮素和去甲肾上腺素水平。NYHA心功能II级的38例患者血浆TNF-α水平为3.2±0.2 SEM pg/ml，NYHA心功能III级的16例患者为4.0±0.3 SEM pg/ml，NYHA心功能IV级的11例患者为5.3±0.9 SEM pg/ml（与NYHA心功能II级相比，p<0.001）。NYHA心功能II级的38例患者血浆IL-6水平为3.1±0.6 SEM pg/ml，NYHA心功能III级的16例患者为5.2±0.8 SEM pg/ml，NYHA心功能IV级的11例患者为13.3±3.9 SEM pg/ml（与NYHA心功能II级相比，p<0.0001；与NYHA心功能III级相比，p<0.0001）。因此，两种细胞因子均随心力衰竭严重程度的增加而升高，但只有IL-6血浆水平在功能更严重的患者中有所不同。TNF-α与TNF可溶性受体II密切相关（r = 0.8，p<0.0001），与血清肌酐中度相关（r = 0.6, p < 0.0001），而IL-6血浆水平与肾功能无统计学关联。在TNF-α与IL-6（r = 0.3，p<0.01）、大内皮素（r = 0.3，p<0.01）和去甲肾上腺素水平（r = 0.4，p<0.001）之间也发现了显著的中度相关性。本研究支持这样的假设，即在心力衰竭中，两种细胞因子TNF-α和IL-6以及神经体液因子在疾病的临床进展中起作用。因此，TNF-α水平而非IL-6水平似乎与并发的肾功能障碍有关。