Experimental studies have shown that cytokine production by the heart may be regulated by sympathetic nervous system stimulation of cardiac beta-adrenergic receptors. Proinflammatory cytokine levels are increased in heart failure, whereas cardiac fixation of 123-I-metaiodobenzylguanidine (MIBG) has been used to study myocardial adrenergic innervation. This study was designed to assess the relation between cardiac MIBG uptake and circulating levels of proinflammatory cytokines in patients with idiopathic dilated cardiomyopathy (IDC). Forty-seven patients (12 women; mean age 56.5 +/- 9 years) with angiographically proved IDC, in New York Heart Association functional classes II to III, and who had left ventricular ejection fraction 30.6 +/- 9.5%, and 20 healthy controls were studied with planar MIBG. The early (10 minutes) and late (4 hours) heart to mediastinum uptake ratio and washout were calculated. Circulating plasma levels of interleukins (IL)-1 and IL-6, tumor necrosis factor-alpha, and solube receptors of TNF (sTNFR) I and II were measured. The patient group had significantly lower values of MIBG uptake at 10 minutes (p <0.001) and 4 hours (p <0.001) and higher washout (p <0.001) than the controls. Late MIBG uptake was significantly correlated with New York Heart Association class (r = -0.42, p = 0.02), left ventricular ejection fraction (r = 0.34, p = 0.01), left ventricular systolic wall stress (r = -0.40, p = 0.05), oxygen consumption at peak exercise (r = 0.32, p = 0.03), IL-1 (r = -0.55, p <0.001), TNF (r = -0.33, p = 0.02), and sTNFRII (r = -0.44, p = 0.001). Multivariate linear regression analysis revealed that MIBG at 4 hours was independently associated with IL-1 levels (p <0.001). Thus, reduced cardiac sympathetic innervation in heart failure is associated with elevated levels of inflammatory cytokines, suggesting that it has a potential inflammatory effect via modulation of the cardiac production of these cytokines.