HEMODYNAMIC, NEUROENDOCRINE AND METABOLIC CORRELATES OF CIRCULATING CYTOKINE CONCENTRATIONS IN CONGESTIVE-HEART-FAILURE

Objectives Increased activity of pro-inflammatory cytokines in the cir culation has been observed in many, though not all, patients with cong estive heart failure. To identify the predictors of cytokine activatio n in congestive heart failure, we assessed the relationship of periphe ral and hepatic venous cytokines to central haemodynamics, neuroendocr ine status and intermediary metabolism in patients with moderate or se vere congestive heart failure. Patients and methods Concentrations of tumour necrosis factor-alpha, soluble tumour necrosis factor-receptor II and interleukin 6 were measured from peripheral and hepatic venous plasma in 58 adult cardiac patients, of whom 44 had congestive heart f ailure, undergoing heart catheterization, echocardiography and assessm ent of selected neuroendocrine and metabolic characteristics. Results Peripheral venous soluble tumour necrosis factor-receptor II was direc tly related to NYHA class (r(s)=0.46, P<0.001) and inversely to 6-min walking distance (r(s)=-0.46, P<0.001). Peripheral venous tumour necro sis factor-alpha was related to 6-min walking distance (r(s)=-0.37, P< 0.01), but like soluble tumour necrosis factor-receptor II, was unrela ted to other haemodynamic and neuroendocrine measurements. Peripheral venous interleukin 6 correlated with NYHA class (r(s)=0.66, P<0.001) a nd 6-min walking distance (r(s)=-0.52, P<0.001). In addition, interleu kin 6 was related to right atrial pressure (r(s)=0.55, P<0.001), pulmo nary artery wedge pressure (r(s)=0.50, P<0.001) and left ventricular e jection fraction (r(s)=-0.39, P<0.01); in multivariate analysis, only right atrial pressure was an independent predictor of interleukin 6 co ncentration (P<0.001). Comparisons between patients with and without c ongestive heart failure showed significantly higher hepatic venous tum our necrosis factor-alpha, soluble tumour necrosis factor-receptor II and interleukin 6 in the heart failure group; the differences in perip heral venous cytokines were less consistent. Conclusions In cardiac pa tients, increased plasma tumour necrosis factor-alpha and soluble tumo ur necrosis factor-receptor II are associated with symptoms of heart f ailure and poor exercise capacity, while the most important predictor of increased interleukin 6 is elevated systemic venous pressure. Diffe rent but still unknown mechanisms may be responsible for the increased release of cytokines in congestive heart failure.