A ROLE OF CYTOKINE IN PROGRESSION OF HEARTFAILRE

先前的研究表明，循环细胞因子（即TNFa）在晚期心力衰竭（HF）患者中增加。我们研究了调节肽，两种天然存在的可溶性TNF受体（sTNF-RI和sTNF-RII）是否在HF患者中增加。这些肽可以预防TNF引起的不良病理后遗症。我们用酶联免疫分析法（ELISA）检测了37例HF患者（NYHA II 16, III 14, IV 7）和年龄匹配的对照组（n=24）的血浆。心衰患者与正常受试者TNFa差异无统计学意义(7.7<正负> 1.7（平均<正负> SEM） vs6.9 <正负> 1.2pg/ml；ns)。然而，心力衰竭患者的可溶性TNF-RI明显高于正常受试者（1629 <正负> 153vs681 <正负> 53pg/ml, p<0.01），心力衰竭患者的可溶性TNF-RII也高于对照组（2124 <正负> 157vs3005 <正负> 196pg/ml, p<0.01）。此外，可溶性TNF-RI随心力衰竭严重程度的增加而增加（正常受试者；681 <正负> 53pg/ml， NYHA II级；1226 <正负> 115pg/ml， NYHA III级；1624 <正负> 207pg/ml， NYHA IV级；2789 <正负> 568pg/ml）。同样，在心衰患者中，可溶性TNF-RII随着症状严重程度的增加而增加（正常受试者；2124 <正负> 157pg/ml， NYHA II类；2555 <正负> 140pg/ml， NYHA III类；2909 <正负> 262pg/ml， NYHA IV类；4500 <正负> 764pg/ml）。溶性TNF R-1水平与溶性TNF R-II水平相关。这些结果提示：1)在HF患者的多种组织中，释放的溶性受体可能通过结合分子和阻止配体与细胞TNF受体结合来抑制TNF的生物活性；2)溶性TNF受体水平可能反映充血性心力衰竭的严重程度。

Previous investigations have suggested that circulating cytokines (i.e., TNFa) are increased in patients with advanced heart failure (HF). We investigated whether regulatory peptides, two types of naturally occurring soluble TNF receptors (sTNF-RI and sTNF-RII) are increased in patients with HF.These peptides can prevent the adverse pathologic sequela caused by TNF.We assayd plasma from 37 patients with HF (NYHA II 16, III 14, IV 7) and the age-matched control subjects(n=24) with Enzyme-Linked Immunoassay (ELISA). TNFa had no significant difference between heart failure patients and normal subjects (7.7<plus-minus> 1.7 (mean<plus-minus> SEM) vs6.9 <plus-minus> 1.2pg/ml ; ns). However, soluble TNF-RI was significantly higher in patients with heart failure than normal subjects (1629 <plus-minus> 153vs681 <plus-minus> 53pg/ml ; p<0.01) and soluble TNF-RII was also higher in patients with heart failure than control subjects (2124 <plus-minus> 157vs3005 <plus-minus> 196pg/ml ; p<0.01). Further, soluble TNF-RI was increased in relation to the severity of heart failure (normal subjects ; 681 <plus-minus> 53pg/ml, NYHA class II ; 1226 <plus-minus> 115pg/ml, NYHA class III ; 1624 <plus-minus> 207pg/ml, NYHA class IV ; 2789 <plus-minus> 568pg/ml). Similarly, there was an increase in soluble TNF-RII with symptomatic severity in heart failure (normal subjects ; 2124 <plus-minus> 157pg/ml, NYHA class II ; 2555 <plus-minus> 140pg/ml, NYHA class III ; 2909 <plus-minus> 262pg/ml, NYHA class IV ; 4500 <plus-minus> 764pg/ml). The levels of soluble TNF R-1 were related to those of soluble TNF R-II in heThese results suggest that 1) in a variety of tissues in HF patients, the released soluble receptors may inhibit TNF bioactivity by binding the molecule and preventing ligand to the cellular TNF receptors and 2) the levels of soluble TNF receptors may reflect the severity of congestive heart failure.