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C-reactive protein contributes to tumor necrosis factor alpha production on monocytes from patients with congestive heart failure

C反应蛋白有助于充血性心力衰竭患者的单核细胞产生肿瘤坏死因子α

基本信息

批准号：
12670701
负责人：
NAKAGOMI Akihiro
金额：
$ 1.6万
依托单位：
Nippon Medical School
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (C)
财政年份：
2000
资助国家：
日本
起止时间：
2000 至 2001
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-12670701/
关键词：
TNF-α C-reactive protein Heart failure 組織因子炎症性サイトカイン C-Reactive Protein

项目摘要

Tumor necrosis factor alpha (TNF), a proinflammatory cytokine with potent negative inotropic properties, is elaborated in patients with advanced congestive heart failure (CHF) and the levels of TNF were correlated well with New York Heart Association (NYHA) functional class (a maker of the degree of CHF).C-reactive protein (CRP), an acute phase reactant, is secreted by hepatocytes in response to interleukin 6 and CRP induces TNF on monocytes. Recently some investigators demonstrated TNF mRNA and protein in the failing human myocardium, suggesting that myocardium itself might produce TNF. On the other hand, monocytes is thought to be the major source of TNF production in response to lipopolysaccharide (LPS), so we hypotheses TNF on monocytes might be responsible for the progressive cardiac decompensation. Peripheral blood mononuclear cells (PBMC) were isolated from 10 normal subjects and 14 patients with CHF (mean EF ; 22.5 %) and were incubated with CRP, LPS and their combination and TNF levels on monocytes were determined using enzyme-linked immunosorbent assay. At the same time, plasma levels of brain natriuretic hormone (BMP ; a maker of CHF degree) were also measured. Basal (Unstimulated), CRP, LPS, and CRP+LPS induced monocyte TNF levels in CHF patients were significantly higher than those in normal subjects. In CHF patients, there was a significant correlation between BNP levels in plasma and basal and monocyte TNF levels induced by CRP+LPS, indicating that TNF on monocytes might be responsible for the progression of CHF.

在晚期充血性心力衰竭(CHF)患者中，肿瘤坏死因子α(TNF)是一种具有强烈负性肌力作用的促炎细胞因子，其水平与纽约心脏协会(NYHA)功能分级(CHF程度的指标)密切相关。C-反应蛋白(CRP)是一种急性时相反应物，由肝细胞分泌，对白细胞介素6(IL-6)作出反应，并诱导单核细胞产生肿瘤坏死因子。最近，一些研究人员在衰竭的人心肌中发现了肿瘤坏死因子的mRNA和蛋白，提示心肌本身可能会产生肿瘤坏死因子。另一方面，单核细胞被认为是内毒素反应产生肿瘤坏死因子的主要来源，因此我们推测单核细胞上的肿瘤坏死因子可能与进行性心脏失代偿有关。从10例正常人和14例CHF患者外周血中分离单个核细胞(PBMC)，分别与C反应蛋白、内毒素及其组合孵育，用双抗体夹心酶联免疫吸附试验检测单核细胞表面肿瘤坏死因子水平。同时检测血浆脑利钠激素(BMP，反映CHF程度的指标)水平。CHF患者基础(未刺激)、C反应蛋白、内毒素及C反应蛋白+内毒素诱导的单核细胞肿瘤坏死因子水平显著高于正常对照组。CHF患者血浆BNP水平与C反应蛋白+内毒素诱导的基础和单核细胞肿瘤坏死因子水平显著相关，提示单核细胞上的肿瘤坏死因子可能参与了心衰的发生发展。