Aspirin-exacerbated respiratory disease (AERD) is explained in part by over-expression of 5-lipoxygenase, leukotriene C4 synthase\n(LTC4S) and the cysteinyl leukotriene (CysLT) receptors (CysLT1 and 2), resulting in constitutive over-production of CysLTs and\nthe hyperresponsiveness to CysLTs that occurs with aspirin ingestion. Increased levels of IL-4 have been found in the sinus mucosa\nand nasal polyps of AERD subjects. Previous studies demonstrated that IL-4 is primarily responsible for the upregulation of LTC4S\nby mast cells and the upregulation of CysLT1 and 2 receptors on many immune cell types. Prostaglandin E2 (PGE2) acts to prevent\nCysLT secretion by inhibiting mast cell and eosinophil activation. PGE2 concentrations are reduced in AERD reflecting diminished\nexpression of cyclooxygenase (COX)-2. IL-4 can inhibit basal and stimulated expression of COX-2 and microsomal PGE synthase\n1 leading to decreased capacity for PGE2 secretion. Thus, IL-4 plays an important pathogenic role in generating the phenotype\nof AERD. This review will examine the evidence supporting this hypothesis and describe a model of how aspirin desensitization\nprovides therapeutic benefit for AERD patients.
Loading....