Immune activation is associated with reduced skeletal muscle mass and physical function in chronic heart failure

Chronic heart failure is characterized by immune activation and increased circulating levels of cytokines. Whether humoral factors contribute to the peripheral manifestations of the heart failure syndrome, such as muscle atrophy and reduced physical work capacity, however, is not clear.

We measured circulating cytokines (tumor necrosis factor-alpha (TNF-alpha), interleukin-6 (IL-6)), their soluble receptors (sTNF-alpha RII, IL-6sR), markers of immune activation (C-reactive protein (CRP)), muscle mass, aerobic capacity and muscle strength in 10 patients with heart failure (mean +/- S.E.; 63 +/- 3 years) and 11 controls (70 +/- 3 years).

Heart failure patients exhibited decreased aerobic capacity (P < 0.01) and leg muscle strength (P < 0.05). Reduced muscle strength persisted in heart failure patients after statistical adjustment for differences in skeletal muscle size. All inflammatory markers were increased in heart failure patients (P < or = 0.05 to P < 0.01) compared to controls, with the exception of TNF-alpha. Despite no group differences in TNF-alpha, higher concentrations of this cytokine were correlated to lower skeletal muscle mass in the combined study population (range of r-values: -0.436 to -0.545; P < 0.05 to P < 0.02), as were IL-6 levels (range of r-values: -0.438 to -0.443; P < 0.05). TNF-alpha, sTNF-alpha RII, IL-6 and CRP showed strong negative relationships to aerobic capacity (range of r-values: -0.579 to -0.751; P < 0.01 to P < 0.001). In addition, elevated levels of IL-6 and TNF-alpha were associated with reduced leg and forearm skeletal muscle strength (range of r-values: -0.440 to -0.674; P < 0.05 to P < 0.01). Finally, correlations between cytokines and functional measures were present when heart failure patients were analyzed separately (range of r-values: -0.646 to -0.673; P < 0.05).

Our results suggest that circulating cytokines are related to both skeletal muscle mass and physical function. These findings provide further evidence to support the hypothesis that immune activation contributes to skeletal muscle atrophy and reduced functional capacity in heart failure patients.