A ROLE OF CYTOKINE IN PROGRESSION OF HEARTFAILRE

以前的研究表明，循环细胞因子（即，在患有晚期心力衰竭（HF）的患者中，TNF α）增加。为探讨心力衰竭（HF）患者血浆中两种天然可溶性TNF受体（sTNF-RI和sTNF-RII）的调节肽是否升高，这些肽是否能预防TNF引起的不良病理后遗症，我们用酶联免疫法（ELISA）检测了37例HF患者（NYHA Ⅱ级16例，Ⅲ级14例，Ⅳ级7例）和24例年龄匹配的对照组血浆中sTNF-RI和sTNF-RII的含量。心力衰竭患者和正常受试者之间的TNF a无显著差异（7.7 <plus-minus>± 1.7（平均<plus-minus>SEM）vs6.9 <plus-minus>± 1.2pg/ml ; ns）。但心力衰竭患者血清可溶性TNF-RI明显高于正常对照组（1629 <plus-minus>± 153 vs 681 <plus-minus>± 53 pg/ml ; p&lt;0.01），可溶性TNF-RII也明显高于正常对照组（2124 <plus-minus>± 157 vs 3005 ± <plus-minus>196 pg/ml ; p&lt;0.01）。此外，可溶性TNF-RI与心力衰竭的严重程度相关（正常人：681 <plus-minus>53 pg/ml，NYHA II级; 1226 <plus-minus>115 pg/ml，NYHA III级; 1624 <plus-minus>207 pg/ml，NYHA IV级; 2789 <plus-minus>568 pg/ml）。类似地，在心力衰竭中，随着症状的严重程度，可溶性TNF-RII也增加（正常受试者; 2124 <plus-minus>± 157 pg/ml，NYHA II级; 2555 <plus-minus>± 140 pg/ml，NYHA III级; 2909 <plus-minus>± 262 pg/ml，NYHA IV级; 4500 <plus-minus>± 764 pg/ml）。结果提示：（1）在心衰患者的多种组织中，可溶性TNF R-1和可溶性TNF R-Ⅱ的水平可能通过结合TNF分子和阻止配体与细胞TNF受体结合而抑制TNF的生物活性;（2）可溶性TNF受体的水平可能反映心衰的严重程度。

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.