Circulating levels of interleukin 18 reflect etiologies of heart failure: Th1/Th2 cytokine imbalance exaggerates the pathophysiology of advanced heart failure

Background: Proinflammatory cytokines such as tumor necrosis factor α play an important role in the pathophysiology of CHF. However, the mechanisms of immune activation in CHF remain unknown. Interleukin (IL)-18, a newly discovered cytokine with pleiotropic activities, is known to induce proinflammatory cytokines, chemokines, nitric oxide, and prostaglandins. Methods and Results: We studied 86 patients with New York Heart Association functional class II–IV heart failure. Mean age was 62 years, 20 were women, and mean left ventricular ejection fraction was 34.8%. Circulating levels of IL-18 and IL-10, high-sensitivity testing for C-reactive protein, and brain natriuretic peptide levels were determined. Serum IL-18 concentrations were significantly higher in patients with NYHA class IV than in patients with classes II and III (P