Induction of functional inducible nitric oxide synthase in monocytes of patients with congestive heart failure. Link with tumour necrosis factor-α

Aims. We studied the induction of monocytic inducible nitric oxide synthase expression and the tumour necrosis factor-α system in patients with congestive heart failure. Methods and Results. Forty-three congestive heart failure patients and 15 healthy subjects were studied. Antigenic tumour necrosis factor-α and its soluble receptors, measured by ELISA, were increased in chronic heart failure and the increase was related to the clinical severity of the syndrome (tumour necrosis factor-α from 8.2 ± 5.2 in NYHA class II to 18.2 ± 7.2 in class III and 26.9 ± 13.2 pg.ml^-1 in class IV, P <0.0001 classes III and IV vs class II; soluble tumour necrosis factor receptor I from 1.0 ± 0.2 in class II to 2.3 ± 1.1 in class III and 5.5 ± 3.2 ng.ml^-1 in class IV, P <0.0001 classes III and IV vs class II; soluble tumour necrosis factor receptor II from 2.7 ± 0.7 in class II to 4.9 ± 1.9 in class III and 8.4 ± 5.0 ng.ml^-1 in class IV, P <0.002 classes III and IV vs class II). Monocytic inducible nitric oxide synthase assessed by Western blot, was expressed only in congestive heart failure patients (13 out of 43). The association among monocytic inducible nitric oxide synthase expression, tumour necrosis factor-α system activation, neurohormones and other clinical parameters was studied. The univariate logistic regression showed that inducible nitric oxide synthase expression was strictly associated with NYHA class (P <0.05), antigenic tumour necrosis factor-α (P <0.01) and its soluble receptors (P <0.05). The multivariate analysis showed that antigenic tumour necrosis factor-α was the only predictor for monocytic inducible nitric oxide synthase expression (P <0.05, RR = 2.75, CI 1.34-5.43). Conclusions. Inducible nitric oxide synthase is expressed in circulating monocytes of patients with severe congestive heart failure. This phenomenon is linked to the activation of the tumour necrosis factor-α system.