Exercise Training in Chronic Heart Failure: Effects on Pro-Inflammatory Markers

BACKGROUND: Acute bouts of exercise have been shown to induce inflammatory cytokine activation and peripheral hypoxia in patients with chronic heart failure (CHF). In this study, we set out to investigate the impact of chronic exercise training on pro-inflammatory cytokines and markers of endothelial damage. METHODS AND RESULTS: We measured tumor necrosis factor alpha (TNFalpha), its soluble TNF-receptors 1 and 2, interleukin 6 (IL-6), soluble e-selectin, soluble intracellular adhesion molecule-1 (sICAM) and sCD14 in 18 patients with CHF and 9 age-matched controls in a randomized cross-over study of 8 weeks of exercise training (5 days/week, submaximal bicycle ergometer training, 30 min/day; calisthenics 9 min/day) versus 8 weeks of rest. At baseline, patients had a lower peak Vo(2) (p=0.009) and a trend for higher levels of e-selectin (p=0.08) and sCD14 (p=0.06), in addition to significantly elevated levels of sICAM (p=0.02), TNFalpha (p=0.02) and TNF-R2 (p=0.002); TNF-R1 and IL-6 were not elevated. Although exercise training was effective and led to an increase in peak Vo(2) in CHF (p<0.003), there was no activation of any of the above variables observed, neither in patients nor controls. CONCLUSIONS: Chronic heart failure is associated with increased levels of TNFalpha and markers of endothelial damage. Whereas acute bouts of exercise have been reported to lead to an increase in pro-inflammatory cytokines and markers of endothelial damage, these effects are not seen when exercise is performed chronically.