BACKGROUND: The effects of inspiratory muscle training on plasma cytokines, C-reactive protein and the soluble apoptosis mediators Fas and Fas ligand in chronic heart failure are unknown. DESIGN AND METHODS: Thirty-eight patients with chronic heart failure, age 57+/-2 years, New York Heart Association classification II-III, were assigned to either a high intensity training group (n=15, age 53+/-2 years) exercised at 60% of sustained maximal inspiratory pressure, or a low intensity training group (n=23, age 59+/-2 years), exercised at 15% of sustained maximal inspiratory pressure, three times per week for 10 weeks. Patients in the high intensity training group and low intensity training group were matched for age, sex and New York Heart Association functional class. Plasma levels of tumor necrosis factor (TNF)-alpha, soluble TNF receptor I, interleukin-6, C-reactive protein, soluble apoptosis mediators Fas and Fas ligand were measured at baseline and at post-inspiratory muscle training. Pulmonary function was assessed by spirometry, exercise capacity by a cardiopulmonary exercise test and the 6 min walk test, whereas dyspnea by the Borg scale after the 6 min walk test. RESULTS: High intensity training group improved inspiratory muscle strength (105.1+/-4.9 vs. 79.8+/-4.7 cmH2O, P<0.001), sustained maximal inspiratory pressure (504.5+/-39.7 vs. 312.5+/-26.5 cmH2O/s/10, P<0.001), forced vital capacity (98.9+/-3.9 vs. 96+/-3.3%, P<0.05), peak VO2 (19.4+/-1.2 vs. 17.3+/-0.9 ml/kg per min, P<0.01), 6 min walk test distance (404.3+/-11.9 vs. 378.2+/-10.4 m, P<0.01) and dyspnea (8.0+/-0.4 vs. 9.2+/-0.4, P<0.01). Circulating TNF-alpha, soluble TNF receptor I, interleukin-6, C-reactive protein, soluble apoptosis mediators Fas and Fas ligand were not significantly altered. Low intensity training group increased only the inspiratory muscle strength (90.3+/-5.9 vs. 80.2+/-5 cmH2O, P<0.01). Comparison between groups was significant for soluble TNF receptor I change (high intensity training group, 5.8+/-0.49 vs. 6.1+/-0.42; low intensity training group, 8.4+/-0.6 vs. 7.8+/-0.6, P<0.01). CONCLUSION: A high intensity inspiratory muscle training program resulted in improvement in functional status of chronic heart failure patients compared with low intensity inspiratory muscle training. Improvement in exercise capacity was not associated with an anti-inflammatory effect, although a beneficial influence on soluble TNF receptor I was recorded. Possible reasons include inadequate level of muscle mass exercise and the low pretraining New York Heart Association class.