title: Interleukin-18 as a therapeutic target in acute myocardial infarction and heart failure.
abstract: Interleukin 18 (IL-18) is a proinflammatory cytokine in the IL-1 family that has been implicated in a number of disease states. In animal models of acute myocardial infarction (AMI), pressure overload, and LPS-induced dysfunction, IL-18 regulates cardiomyocyte hypertrophy and induces cardiac contractile dysfunction and extracellular matrix remodeling. In patients, high IL-18 levels correlate with increased risk of developing cardiovascular disease (CVD) and with a worse prognosis in patients with established CVD. Two strategies have been used to counter the effects of IL-18:IL-18 binding protein (IL-18BP), a naturally occurring protein, and a neutralizing IL-18 antibody. Recombinant human IL-18BP (r-hIL-18BP) has been investigated in animal studies and in phase I/II clinical trials for psoriasis and rheumatoid arthritis. A phase II clinical trial using a humanized monoclonal IL-18 antibody for type 2 diabetes is ongoing. Here we review the literature regarding the role of IL-18 in AMI and heart failure and the evidence and challenges of using IL-18BP and blocking IL-18 antibodies as a therapeutic strategy in patients with heart disease.
authors.affiliation: Department of Physiology and Biophysics, Virginia Commonwealth University, Richmond, Virginia, United States of America.
authors.forename: Laura C
authors.initials: LC
authors.lastname: O'Brien
authors.affiliation: Victoria Johnson Research Laboratories, Virginia Commonwealth University, Richmond, Virginia, United States of America Virginia Commonwealth University Pauley Heart Center, School of Medicine, Virginia Commonwealth University, Richmond, Virginia, United States of America Pharmacotherapy and Outcome Sciences, School of Pharmacy, Virginia Commonwealth University, Richmond, Virginia, United States of America.
authors.forename: Eleonora
authors.initials: E
authors.lastname: Mezzaroma
authors.affiliation: Victoria Johnson Research Laboratories, Virginia Commonwealth University, Richmond, Virginia, United States of America Virginia Commonwealth University Pauley Heart Center, School of Medicine, Virginia Commonwealth University, Richmond, Virginia, United States of America Pharmacotherapy and Outcome Sciences, School of Pharmacy, Virginia Commonwealth University, Richmond, Virginia, United States of America.
authors.forename: Benjamin W
authors.initials: BW
authors.lastname: Van Tassell
authors.affiliation: Victoria Johnson Research Laboratories, Virginia Commonwealth University, Richmond, Virginia, United States of America Virginia Commonwealth University Pauley Heart Center, School of Medicine, Virginia Commonwealth University, Richmond, Virginia, United States of America.
authors.forename: Carlo
authors.initials: C
authors.lastname: Marchetti
authors.affiliation: Victoria Johnson Research Laboratories, Virginia Commonwealth University, Richmond, Virginia, United States of America Virginia Commonwealth University Pauley Heart Center, School of Medicine, Virginia Commonwealth University, Richmond, Virginia, United States of America.
authors.forename: Salvatore
authors.initials: S
authors.lastname: Carbone
authors.affiliation: Department of Physiology and Biophysics, Virginia Commonwealth University, Richmond, Virginia, United States of America Victoria Johnson Research Laboratories, Virginia Commonwealth University, Richmond, Virginia, United States of America Virginia Commonwealth University Pauley Heart Center, School of Medicine, Virginia Commonwealth University, Richmond, Virginia, United States of America.
authors.forename: Antonio
authors.initials: A
authors.lastname: Abbate
authors.affiliation: Victoria Johnson Research Laboratories, Virginia Commonwealth University, Richmond, Virginia, United States of America Virginia Commonwealth University Pauley Heart Center, School of Medicine, Virginia Commonwealth University, Richmond, Virginia, United States of America.
authors.forename: Stefano
authors.initials: S
authors.lastname: Toldo
mesh_terms: D000818:Animals; D017209:Apoptosis; D006331:Heart Diseases / Q000378:metabolism*; D006801:Humans; D020382:Interleukin-18 / Q000037:antagonists & inhibitors / Q000378:metabolism*; D009200:Myocardial Contraction; D011943:Receptors, Adrenergic, beta / Q000378:metabolism
chemical_list: D020382:Interleukin-18; D011943:Receptors, Adrenergic, beta