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

OBJECTIVES The study objective was to assess the cardiac expression of interleukin-6 (IL6) and its receptor (IL6R) in advanced heart failure. BACKGROUND While IL6 plasma levels are elevated and associated with an impaired prognosis in advanced heart failure, little is known about the intracardiac expression of the IL6 system. METHODS Heart tissue was obtained from 20 patients (n=10, idiopathic dilated cardiomyopathy, age 44+/-15 years; n=10, ischemic cardiomyopathy, age 55+/-8 years) at the time of transplantation. Left and right ventricular tissue was subjected to in situ hybridization, Northern blot analysis, and RT-PCR. Signals were quantified by densitometric scanning and corrected for G3PDH-mRNA levels. Right ventricular biopsy specimens (n=11) of patients with arrhythmias and normal cardiac function served as controls. In addition, data were correlated with cardiac catheterization and echocardiography data obtained at transplant evaluation. RESULTS Ventricular IL6 and IL6R transcripts were detected in all explant specimens examined. Expression of both mRNA species was higher than in controls (P=0.001). Left ventricular IL6 mRNA levels correlated positively with 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 ventricular IL6 mRNA levels correlated inversely with cardiac index (r=-0.48; P=0.05). IL6R expression did not correlate with hemodynamic data. CONCLUSIONS In advanced heart failure, cardiac IL6/IL6R mRNA expression is increased and may play a role in the pathophysiology of advanced heart failure.