Interleukin-18 in patients with congestive heart failure: Induction of atrial natriuretic peptide gene expression

Activated inflammatory responses appear to play a role in the development o f congestive heart failure (CHF). We investigated interleukin-18 (IL-18), w hich is a cytokine synthesized by activated macrophage, changes in patients with CHF. We evaluated I I Japanese patients with angina pectoris (n=4) or CHF (n=7). Blood was sampled immediately after admission and at 1, 2, 3, 6 , and 9 hours after admission and then every 12 hours until 5 days after ad mission. Plasma IL-18 concentrations were measured by an enzyme-linked immu nosorbent assay. Expression of atrial natriuretic peptide (ANP) mRNA and pr otein synthesis was examined in cardiac myocyte by stimulation of IL-18. Pl asma IL-18 concentration was significantly higher in patients with CHF than in 15 healthy volunteers (51 +/- 21 pg/mL, and 28 +/- 11 pg/mL, respective ly, P <0.05). Increased expression of ANP mRNA was demonstrated in IL-18 tr eated myocytes. Protein synthesis in myocytes was increased by IL-18 in a d ose-dependent manner. Increased secretion of IL-18 is induced in patients w ith CHF and correlates with the severity of myocardial damage and dysfuncti on.