Nozaki N, Yamaguchi S, Shirakabe M, Nakamura H, Tomoike H
First Department of Internal Medicine, Yamagata University Medical School, Japan.
Jpn Circ J. 1997 Aug;61(8):657-64. doi: 10.1253/jcj.61.657.
The level of tumor necrosis factor alpha (TNF-alpha) is increased in patients with congestive heart failure and may play an important role in the development and progression of heart failure. Two types of TNF receptor (TNF-RI and TNF-RII) are expressed in virtually every cell and have different biologic roles. Soluble forms of the two receptors (sTNF-RI and sTNF-RII) have been identified as extracellular domain fragments. Serum levels of TNF-alpha, sTNF-RI and sTNF-RII were measured in 66 patients with heart failure and 27 control subjects using an enzyme-linked immunosorbent assay (ELISA). Hemodynamic variables, norepinephrine, atrial natriuretic peptide (ANP), and brain natriuretic peptide (BNP) were evaluated. TNF-alpha was significantly higher in patients with heart failure than in controls subjects (9.4 +/- 1.4 vs 4.8 +/- 0.8 pg/ml; p < 0.05). sTNF-RI and -RII were significantly increased in relation to the severity of heart failure (control subjects, 0.66 +/- 0.04 and 1.97 +/- 0.15 ng/ml; NYHA class II, 1.10 +/- 0.08 and 2.28 +/- 0.12 ng/ml; NYHA class III, 1.63 +/- 0.22 and 3.00 +/- 0.24 ng/ml; NYHA class IV, 2.78 +/- 0.46 and 4.52 +/- 0.62 ng/ml, respectively). In 9 patients whose clinical symptoms improved after treatment, the levels of sTNF-RI and -RII decreased by 17.3 +/- 5.7% (p < 0.05) and 22.1 +/- 6.9% (p < 0.05), respectively. There were significant positive correlations between sTNF-RI and -RII and mean pulmonary pressure (r = 0.69 and r = 0.61; p < 0.001) and mean capillary wedge pressure (r = 0.65 and r = 0.54; p < 0.001 and p < 0.01, respectively), but not with left ventricular end-diastolic volume or ejection fraction (NS). sTNF-RI and -RII were also significantly positively correlated with plasma levels of norepinephrine (r = 0.75 and r = 0.50; p < 0.001 and p < 0.05), ANP (r = 0.72 and r = 0.70; p < 0.001), and BNP (r = 0.60 and r = 0.60; p < 0.001). In conclusion, soluble TNF receptors are increased in proportion to the severity of congestive heart failure and may reflect the current status of congestive heart failure rather than the level of left ventricular dysfunction.
充血性心力衰竭患者的肿瘤坏死因子α（TNF-α）水平升高，其可能在心力衰竭的发生和发展中起重要作用。两种类型的TNF受体（TNF-RI和TNF-RII）几乎在每个细胞中均有表达，且具有不同的生物学作用。已将这两种受体的可溶性形式（sTNF-RI和sTNF-RII）鉴定为细胞外结构域片段。采用酶联免疫吸附测定（ELISA）法检测了66例心力衰竭患者和27例对照者的血清TNF-α、sTNF-RI和sTNF-RII水平。评估了血流动力学变量、去甲肾上腺素、心房利钠肽（ANP）和脑利钠肽（BNP）。心力衰竭患者的TNF-α水平显著高于对照者（9.4±1.4对4.8±0.8 pg/ml；p<0.05）。sTNF-RI和-RII与心力衰竭的严重程度显著相关（对照者，0.66±0.04和1.97±0.15 ng/ml；纽约心脏协会II级，1.1±0.08和2.28±0.12 ng/ml；纽约心脏协会III级，1.63±0.22和3.00±0.24 ng/ml；纽约心脏协会IV级，分别为2.78±0.46和4.52±0.62 ng/ml）。在9例治疗后临床症状改善的患者中，sTNF-RI和-RII水平分别下降了17.3±5.7%（p<0.05）和22.1±6.9%（p<0.05）。sTNF-RI和-RII与平均肺动脉压（r=0.69和r=0.61；p<0.001）和平均毛细血管楔压（r=0.65和r=0.54；分别为p<0.001和p<0.01）之间存在显著正相关，但与左心室舒张末期容积或射血分数无关（无显著性差异）。sTNF-RI和-RII与血浆去甲肾上腺素水平（r=0.75和r=0.50；p<0.001和p<0.05）、ANP（r=0.72和r=0.70；p<0.001）和BNP（r=0.60和r=0.60；p<0.001）也显著正相关。总之，可溶性TNF受体与充血性心力衰竭的严重程度成比例增加，可能反映充血性心力衰竭的当前状态，而非左心室功能障碍的程度。
