Proinflammatory cytokines are capable of modulating cardiovascular function by a variety of mechanisms. These cytokines are elevated in patients with severe heart failure, but changes in mild or moderate heart failure have not been reported. Therefore, simultaneous arterial and coronary sinus concentrations of interleukin-1alpha, soluble interleukin-2 receptor, interleukin-6, and tumor necrosis factor-alpha were measured in 78 patients with New York Heart Association functional class II to IV heart failure and compared with 17 healthy volunteers. Concentrations of interleukin-1alpha, soluble interleukin-2 receptor, and interleukin-6 were determined by a "sandwich" enzyme-linked immunosorbent assay and tumor necrosis factor-alpha by tissue culture technique. There were no statistical differences in interleukin-1alpha, soluble interleukin-2 receptor, or tumor necrosis factor-alpha concentrations in mild to moderate heart failure versus control subjects. Interleukin-6 was significantly elevated, 75 +/- 16 versus 0.4 +/- 0.4pg/ml (p = 0.002). Cytokine concentrations did not differ by heart failure etiology. Paired arterial and coronary sinus concentrations were not significantly different. Soluble interleukin-2 receptor concentrations were significantly correlated with New York Heart Association functional class (r = 0.59, p = 0.04) and negatively associated with exercise tolerance time (r = -0.59, p = 0.007). Thus, interleukin-6 is significantly elevated in mild or moderate heart failure.