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(Circulation. 2008;117:2577-2579.)
© 2008 American Heart Association, Inc.

Editorial

Inflammation and Cardiovascular Disease

Role of the Interleukin-1 Receptor Antagonist

William F. Fearon, MD; Douglas T. Fearon, MD

From the Division of Cardiovascular Medicine, Stanford University Medical Center (W.F.F.), Stanford, Calif, and Wellcome Trust Immunology Unit, University of Cambridge (D.T.F.), Cambridge, United Kingdom.

Correspondence to William F. Fearon, MD, Division of Cardiovascular Medicine, Stanford University Medical Center, 300 Pasteur Dr, H2103, Stanford, CA 94305. E-mail wfearon@stanford.edu

Key Words: Editorials • atherosclerosis • coronary disease • inflammation

An extract of the first 250 words of the full text is provided, because this article has no abstract.

	Introduction

 
Inflammation plays an important role in the development and progression of a variety of cardiovascular conditions, most notably coronary atherosclerosis and congestive heart failure.^1,2 A number of inflammatory molecules have been implicated in these processes, including interleukin-1 (IL-1). The IL-1 gene family consists of 3 proteins, IL-1, IL-1β, and IL-1 receptor antagonist (IL-1ra). IL-1 and IL-1β exert their similar effects by binding to the IL-1 type I receptor. The IL-1 type II receptor also binds IL-1 and IL-1β but acts as a decoy receptor and is not involved in signal transduction, thereby counterbalancing the inflammatory effects of IL-1 and IL-1β. IL-1ra is an endogenous inhibitor of IL-1 and IL-1β, which competitively binds to the IL-1 type I receptor without activating it.³

Article p 2662

Both IL-1 and IL-1ra are produced by endothelial cells, smooth muscle cells, and macrophages. IL-1 secretion is induced by microbial products that stimulate toll-like receptors and by certain endogenous triggers, such as uric acid produced during cell death. Both types of agonists stimulate a cytosolic complex of proteins termed the inflammasome, which activates caspase-1 to enable secretion of IL-1β. The potential of this IL-1β pathway for systemic inflammation is demonstrated not only by gout but also by the clinical effects of activating mutations in cryopyrin (also known as NALP3 or CIAS1), one of the inflammasome components, which causes familial cold autoinflammatory syndrome, Muckle-Wells syndrome, and neonatal-onset multisystem inflammatory disease.⁴

	Cardiac-Related Effects of IL-1 and IL-1ra

 
Circulating levels of IL-1 are associated with the presence of traditional cardiac risk factors, such as . . . [Full Text of this Article]