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.