title: 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.
abstract: BACKGROUND
  An altered IL-18 pathway in heart failure (HF) has recently been described and this cytokine was shown to be 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 regulate cardiovascular homeostasis. The aim of the study was to verify the ability of IL-18 to induce B-type natriuretic peptide synthesis in vitro and to analyse the relationship between these two molecules in plasma in vivo from acute HF patients.
  
  
  RESULTS
  We demonstrated the ability of IL-18 to directly stimulate a murine cardiomyocyte cell line to express 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-type natriuretic peptide plasma levels was found in non-overloaded acute HF patients, and in subgroups of acute HF patients with diabetes and coronary artery disease. Acute HF patients with renal failure had significantly higher IL-18 plasma levels than 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 synthesis in vitro and outlines the relationship between the two molecules in acute HF patients with an ongoing inflammatory status.
authors.affiliation: 1 Emergency Department, Sant'Andrea Hospital, II Faculty of Medicine and Psychology, "LaSapienza" Rome University, Rome, Italy.
authors.forename: Salvatore
authors.initials: S
authors.lastname: Di Somma
authors.affiliation: 1 Emergency Department, Sant'Andrea Hospital, II Faculty of Medicine and Psychology, "LaSapienza" Rome University, Rome, Italy.
authors.forename: Valerio
authors.initials: V
authors.lastname: Pittoni
authors.affiliation: 2 Molecular and Clinical Medicine, Sant'Andrea Hospital, II Faculty of Medicine and Psychology - "LaSapienza" Rome University, Rome, Italy.
authors.forename: Salvatore
authors.initials: S
authors.lastname: Raffa
authors.affiliation: 1 Emergency Department, Sant'Andrea Hospital, II Faculty of Medicine and Psychology, "LaSapienza" Rome University, Rome, Italy.
authors.forename: Laura
authors.initials: L
authors.lastname: Magrini
authors.affiliation: 1 Emergency Department, Sant'Andrea Hospital, II Faculty of Medicine and Psychology, "LaSapienza" Rome University, Rome, Italy.
authors.forename: Giulia
authors.initials: G
authors.lastname: Gagliano
authors.affiliation: 1 Emergency Department, Sant'Andrea Hospital, II Faculty of Medicine and Psychology, "LaSapienza" Rome University, Rome, Italy.
authors.forename: Rossella
authors.initials: R
authors.lastname: Marino
authors.affiliation: 2 Molecular and Clinical Medicine, Sant'Andrea Hospital, II Faculty of Medicine and Psychology - "LaSapienza" Rome University, Rome, Italy.
authors.forename: Valerio
authors.initials: V
authors.lastname: Nobili
authors.affiliation: 2 Molecular and Clinical Medicine, Sant'Andrea Hospital, II Faculty of Medicine and Psychology - "LaSapienza" Rome University, Rome, Italy.
authors.forename: Maria Rosaria
authors.initials: MR
authors.lastname: Torrisi
mesh_terms: D000208:Acute Disease; D000368:Aged; D000369:Aged, 80 and over; D000818:Animals; D015415:Biomarkers / Q000378:metabolism; D002478:Cells, Cultured; D004195:Disease Models, Animal; D005260:Female; D005786:Gene Expression Regulation; D006333:Heart Failure / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D006801:Humans; D020382:Interleukin-18 / Q000096:biosynthesis / Q000235:genetics*; D008297:Male; D051379:Mice; D008856:Microscopy, Fluorescence; D008875:Middle Aged; D032383:Myocytes, Cardiac / Q000378:metabolism* / Q000473:pathology; D020097:Natriuretic Peptide, Brain / Q000096:biosynthesis / Q000235:genetics*; D012333:RNA, Messenger / Q000235:genetics*; D060888:Real-Time Polymerase Chain Reaction
chemical_list: D015415:Biomarkers; D020382:Interleukin-18; D012333:RNA, Messenger; D020097:Natriuretic Peptide, Brain
keywords: Heart failure; hormones; inflammation; interleukins