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

Abstract

Background: Proinflammatory cytokines such as tumor necrosis factor alpha 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 <.001). The serum level of IL-18 and the ratio of IL-18 to IL-10 were greater in patients with ischemic cardiomyopathy than in those with dilated cardiomyopathy.

Conclusions: Th1/Th2 cytokine imbalance exists in patients with advanced CHF according to various etiologies of CHF. The findings suggest an important role for IL-18 in the pathophysiology of CHF and provide a direction for more specific immunomodulating therapy.