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

Aims We studied the induction of monocytic inducible nitric oxide synthase expression and the tumour necrosis factor-alpha system in patients with con gestive heart failure. Methods and Results Forty-three congestive heart failure patients and 15 he althy subjects were studied. Antigenic tumour necrosis factor-alpha and its soluble receptors, measured by ELISA. were increased in chronic heart fail ure and the increase was related to the clinical severity of the syndrome ( tumour necrosis factor-a 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 I II 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) i n class IV, P < 0.0001 classes III and IV vs class II; soluble tumour necro sis 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 b lot, was expressed only in congestive heart failure patients (13 out of 43) . The association among monocytic inducible nitric oxide synthase expressio n, tumour necrosis factor-alpha system activation, neurohormones and other clinical parameters was studied. The univariate logistic regression showed that inducible nitric oxide synthase expression was strictly associated wit h NYHA class (P < 0.05), antigenic tumour necrosis factor-alpha (P < 0.01) and its soluble receptors (P < 0.05). The multivariate analysis showed that antigenic tumour necrosis factor-alpha was the only predictor for monocyti c 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 mon ocytes of patients with severe congestive heart failure. This phenomenon is linked to the activation of the tumour necrosis factor-alpha system. (C) 1 999 The European Society of Cardiology.