IL-18 stimulates B-type natriuretic peptide synthesis by cardiomyocytes in vitro and its plasma levels correlate with B-type natriuretic peptide in non-overloaded acute heart failure patients

Background: An altered IL-18 pathway in heart failure (HF) has recently been described and this cytokine was shown tobe of clinical and prognostic utility. Cardiomyocytes are a target of this cytokine which exerts inflammatory, hypertrophic,and profibrotic activities. B-type natriuretic peptide is a cardiac hormone produced in response to cardiac filling to regulatecardiovascular homeostasis. The aim of the study was to verify the ability of IL-18 to induce B-type natriuretic peptidesynthesis in vitro and to analyse the relationship between these two molecules in plasma in vivo from acute HF patients.Methods and Results: We demonstrated the ability of IL-18 to directly stimulate a murine cardiomyocyte cell line toexpress the B-type natriuretic peptide gene, synthesize the relative protein through a PI3K-AKT-dependent transduction,and induce a cell secretory phenotype with B-type natriuretic peptide release. A correlation between IL-18 and B-typenatriuretic peptide plasma levels was found in non-overloaded acute HF patients, and in subgroups of acute HF patientswith diabetes and coronary artery disease. Acute HF patients with renal failure had significantly higher IL-18 plasma levelsthan patients without. IL-18 plasma levels were correlated with C-reactive protein plasma levels.Conclusions: This study provides the first evidence of the ability of IL-18 to induce B-type natriuretic peptide synthesisin vitro and outlines the relationship between the two molecules in acute HF patients with an ongoing inflammatory status.