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Interleukin-1 in myocardial infarction

DISCOVERIES (ISSN 2359-7232), 2015, January-March issue

CITATION: 

Frangogiannis NG. Interleukin-1 in cardiac injury, repair, and remodeling: pathophysiologic and translational concepts. Discoveries 2015, Jan-Mar; 3(1): e41. DOI: 10.15190/d.2015.33

 Submitted: March 24, 2015; AcceptedMarch 27, 2015Published: March 31, 2015;

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Interleukin-1 in cardiac injury, repair, and remodeling: pathophysiologic and translational concepts

Nikolaos G. Frangogiannis*


The Wilf Family Cardiovascular Research Institute, Department of Medicine (Cardiology), Albert Einstein College of Medicine, Bronx NY, USA

*Correspondence to: Nikolaos G. Frangogiannis, MD, Chair in Cardiovascular Medicine, The Wilf Family Cardiovascular Research Institute, Albert Einstein College of Medicine 1300 Morris Park Avenue Forchheimer G46B, Bronx NY 10461; Phone: 718-430-3546; Fax: 718-430-8989; Email: nikolaos.frangogiannis@einstein.yu.edu

Abstract

In the infarcted myocardium, necrotic cardiomyocytes release danger signals activating an intense inflammatory reaction that serves to clear the wound from dead cells and matrix debris, but may also extend injury. A growing body of evidence suggests an important role for members of the Interleukin (IL)-1 family in injury, repair and remodeling of the infarcted heart. This review manuscript discusses the pathophysiologic functions of IL-1 in the infarcted and remodeling myocardium and its potential role as a therapeutic target in patients with myocardial infarction. Dead cardiomyocytes release IL-1alpha that may function as a crucial alarmin triggering the post-infarction inflammatory reaction. IL-1alpha is markedly upregulated in the infarcted myocardium; activation of the inflammasome in both cardiomyocytes and interstitial cells results in release of bioactive IL-1alpha in the infarcted area. Binding of IL-1 to the type 1 receptor triggers an inflammatory cascade, inducing recruitment of pro-inflammatory leukocytes and stimulating a matrix-degrading program in fibroblasts, while delaying myofibroblast conversion. IL-1 mediates dilative remodeling following infarction and may play a role in the pathogenesis of post-infarction heart failure. As the wound is cleared from dead cells and matrix debris, endogenous inhibitory signals suppress the IL-1 response resulting in repression of inflammation and resolution of the inflammatory infiltrate. Other members of the IL-1 family (such as IL-18 and IL-33) are also implicated in regulation of the inflammatory and reparative response following myocardial infarction. IL-18 may participate in pro-inflammatory signaling, whereas IL-33 may exert cytoprotective effects. Early clinical trials suggest that IL-1 blockade may be a promising therapeutic strategy for patients with myocardial infarction.

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