Activation of the cardiac interleukin-6 system in advanced heart failure

Objectives: The study objective was to assess the cardiac expression of int erleukin-6 (IL6) and its receptor (IL6R) in advanced heart failure. Backgro und: While IL6 plasma levels are elevated and associated with an impaired p rognosis in advanced heart failure, little is known about the intracardiac expression of the IL6 system. Methods: Heart tissue was obtained from 20 pa tients (n = 10, idiopathic dilated cardiomyopathy, age 44 +/- 15 years; n = 10, ischemic cardiomyopathy, age 55 +/- 8 years) at the time of transplant ation. Left and right ventricular tissue was subjected to in situ hybridiza tion, Northern blot analysis, and RT-PCR. Signals were quantified by densit ometric scanning and corrected for G3PDH-mRNA levels. Right ventricular bio psy specimens (n = 11) of patients with arrhythmias and normal cardiac func tion served as controls. In addition, data were correlated with cardiac cat heterization and echocardiography data obtained at transplant evaluation. R esults: Ventricular IL6 and IL6R transcripts were detected in all explant s pecimens examined. Expression of both mRNA species was higher than in contr ols (P = 0.001). Left ventricular IL6 mRNA levels correlated positively wit h heart rate (r = 0.77; P = 0.009), pulmonary capillary wedge pressure (r = 0.53; P = 0.03), right atrial pressure (r 0.77; P = 0.003), and inversely with left ventricular ejection fraction (r = -0.61; P = 0.03). Right ventri cular IL6 mRNA levels correlated inversely with cardiac index (r = -0.48; P = 0.05). IL6R expression did not correlate with hemodynamic data. Conclusi ons: In advanced heart failure, cardiac IL6/IL6R mRNA expression is increas ed and may play a role in the pathophysiology of advanced heart failure. (C ) 2001 European Society of Cardiology. All rights reserved.