Adamopoulos Stamatis, Parissis John, Karatzas Dimitrios, Kroupis Christos, Georgiadis Michael, Karavolias George, Paraskevaidis John, Koniavitou Katerina, Coats Andrew J S, Kremastinos Dimitrios Th
Second Department of Cardiovascular Medicine, Onassis Cardiac Surgery Center, Athens, Greece.
J Am Coll Cardiol. 2002 Feb 20;39(4):653-63. doi: 10.1016/s0735-1097(01)01795-8.
We sought to investigate the effects of physical training on circulating proinflammatory cytokines and the soluble apoptosis mediators Fas (sFas) and Fas ligand (sFasL) in patients with chronic heart failure (CHF).
Recent investigations have shown an overexpression of circulating proinflammatory cytokines and soluble apoptosis mediators in patients with CHF, which may be related to their exercise intolerance and clinical deterioration.
Plasma levels of tumor necrosis factor-alpha (TNF-alpha), soluble TNF receptors I and II (sTNF-RI and sTNF-RII, respectively), interleukin-6 (IL-6), soluble IL-6 receptor (sIL-6R), sFas and sFasL were measured in 24 patients with stable CHF (New York Heart Association functional class II/III; left ventricular ejection fraction 23.2 +/- 1.3%) and in 20 normal control subjects before and after a 12-week program of physical training in a randomized, crossover design. Functional status of patients with CHF was evaluated by using a cardiorespiratory exercise test to measure peak oxygen consumption (VO2max).
Physical training produced a significant reduction in plasma levels of TNF-alpha (7.5 +/- 1.0 pg/ml vs. 4.6 +/- 0.7 pg/ml, p < 0.001), sTNF-RI (3.3 +/- 0.2 ng/ml vs. 2.7 +/- 0.2 ng/ml, p < 0.005), sTNF-RII (2.6 +/- 0.2 ng/ml vs. 2.3 +/- 0.2 ng/ml, p = 0.06), IL-6 (8.3 +/- 1.2 pg/ml vs. 5.9 +/- 0.8 pg/ml, p < 0.005), sIL-6R (34.0 +/- 3.0 ng/ml vs. 29.2 +/- 3.0 ng/ml, p < 0.01), sFas (5.5 +/- 0.7 ng/ml vs. 4.5 +/- 0.8 ng/ml, p = 0.05) and sFasL (34.9 +/- 5.0 pg/ml vs. 25.2 +/- 4.0 pg/ml, p < 0.05), as well as a significant increase in VO2max (16.3 +/- 0.7 ml/kg per min vs. 18.7 +/- 0.8 ml/kg per min, p < 0.001). Good correlations were found between a training-induced increase in VO2max and a training-induced reduction in levels of the proinflammatory cytokine TNF-alpha (r = -0.54, p < 0.01) and the apoptosis inducer sFasL (r = -0.57, p < 0.005) in patients with CHF. In contrast, no significant difference in circulating cytokines and apoptotic markers was found with physical training in normal subjects.
Physical training reduces plasma levels of proinflammatory cytokines and the sFas/sFasL system in patients with CHF. These immunomodulatory effects may be related to the training-induced improvement in functional status of patients with CHF.
我们试图研究体育锻炼对慢性心力衰竭（CHF）患者循环促炎细胞因子以及可溶性凋亡介质Fas（sFas）和Fas配体（sFasL）的影响。
最近的研究表明，CHF患者循环促炎细胞因子和可溶性凋亡介质存在过表达，这可能与他们的运动不耐受和临床病情恶化有关。
采用随机交叉设计，对24例稳定期CHF患者（纽约心脏协会心功能II/III级；左心室射血分数23.2±1.3%）和20名正常对照者在进行为期12周的体育锻炼计划前后，测定血浆肿瘤坏死因子-α（TNF-α）、可溶性TNF受体I和II（分别为sTNF-RI和sTNF-RII）、白细胞介素-6（IL-6）、可溶性IL-6受体（sIL-6R）、sFas和sFasL的水平。通过心肺运动试验测量峰值耗氧量（VO2max）来评估CHF患者的功能状态。
体育锻炼使CHF患者血浆TNF-α水平显著降低（7.5±1.0 pg/ml对4.6±0.7 pg/ml，p<0.001）、sTNF-RI水平显著降低（3.3±0.2 ng/ml对2.7±0.2 ng/ml，p<0.005）、sTNF-RII水平显著降低（2.6±0.2 ng/ml对2.3±0.2 ng/ml，p = 0.06）、IL-6水平显著降低（8.3±1.2 pg/ml对5.9±0.8 pg/ml，p<0.005）、sIL-6R水平显著降低（34.0±3.0 ng/ml对29.2±3.0 ng/ml，p<0.01）、sFas水平显著降低（5.5±0.7 ng/ml对4.5±0.8 ng/ml，p = 0.05）以及sFasL水平显著降低（34.9±5.0 pg/ml对25.2±4.0 pg/ml，p<0.05），同时VO2max显著增加（16.3±0.7 ml/kg每分钟对18.7±0.8 ml/kg每分钟，p<0.001）。在CHF患者中，训练诱导的VO2max增加与训练诱导的促炎细胞因子TNF-α水平降低（r = -0.54，p<0.01）以及凋亡诱导剂sFasL水平降低（r = -0.57，p<0.005）之间存在良好的相关性。相比之下，正常受试者进行体育锻炼后，循环细胞因子和凋亡标志物无显著差异。
体育锻炼可降低CHF患者血浆促炎细胞因子水平以及sFas/sFasL系统水平。这些免疫调节作用可能与训练诱导的CHF患者功能状态改善有关。
