Table of Contents
Journal of Allergy
Volume 2012 (2012), Article ID 182090, 9 pages
http://dx.doi.org/10.1155/2012/182090
Review Article

Interleukin-4 in the Generation of the AERD Phenotype: Implications for Molecular Mechanisms Driving Therapeutic Benefit of Aspirin Desensitization

1Asthma and Allergic Disease Center, Beirne Carter B. Center for Immunology Research, University of Virginia Health System, Charlottesville, VA 22908, USA
2Department of Medicine, University of Virginia Health System, Charlottesville, VA 22908, USA
3Department of Otolaryngology—Head and Neck Surgery, University of Virginia Health System, Charlottesville, VA 22908, USA

Received 1 July 2011; Accepted 4 October 2011

Academic Editor: Hae-Sim Park

Copyright © 2012 John W. Steinke et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Abstract

Aspirin-exacerbated respiratory disease (AERD) is explained in part by over-expression of 5-lipoxygenase, leukotriene C4 synthase (LTC4S) and the cysteinyl leukotriene (CysLT) receptors (CysLT1 and 2), resulting in constitutive over-production of CysLTs and the hyperresponsiveness to CysLTs that occurs with aspirin ingestion. Increased levels of IL-4 have been found in the sinus mucosa and nasal polyps of AERD subjects. Previous studies demonstrated that IL-4 is primarily responsible for the upregulation of LTC4S by mast cells and the upregulation of CysLT1 and 2 receptors on many immune cell types. Prostaglandin E2 (PGE2) acts to prevent CysLT secretion by inhibiting mast cell and eosinophil activation. PGE2 concentrations are reduced in AERD reflecting diminished expression of cyclooxygenase (COX)-2. IL-4 can inhibit basal and stimulated expression of COX-2 and microsomal PGE synthase 1 leading to decreased capacity for PGE2 secretion. Thus, IL-4 plays an important pathogenic role in generating the phenotype of AERD. This review will examine the evidence supporting this hypothesis and describe a model of how aspirin desensitization provides therapeutic benefit for AERD patients.