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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 E<jats:sub>2<\/jats:sub>(PGE<jats:sub>2<\/jats:sub>) acts to prevent CysLT secretion by inhibiting mast cell and eosinophil activation. PGE<jats:sub>2<\/jats:sub>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 PGE<jats:sub>2<\/jats:sub>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.<\/jats:p>","DOI":"10.1155\/2012\/182090","type":"journal-article","created":{"date-parts":[[2012,1,3]],"date-time":"2012-01-03T23:18:37Z","timestamp":1325632717000},"page":"1-9","source":"Crossref","is-referenced-by-count":7,"title":["Interleukin-4 in the Generation of the AERD Phenotype: Implications for Molecular Mechanisms Driving Therapeutic Benefit of Aspirin Desensitization"],"prefix":"10.1155","volume":"2012","author":[{"given":"John W.","family":"Steinke","sequence":"first","affiliation":[{"name":"Asthma and Allergic Disease Center, Beirne Carter B. 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