Role of cysteinyl-leukotrienes in the pathogenesis of nasal polyposis in patients with asthma

Abstract

Cysteinyl leukotrienes (CysLTs: leukotrienes C4, D4, and E4) have long been implicated in the pathogenesis of allergic diseases such as asthma. CysLTs are potent bronchoconstrictors that have the additional effects of edema, mucous secretion, and eosinophilic accumulation, and airway remodeling. LTE4 has been identified as a major metabolite of LTC4, and urinary LTE4 (U-LTE4) is considered as the most reliable analytic parameter for monitoring the endogenous synthesis of CysLTs. From our extensive study of U-LTE4 in adult asthma, we identified four factors for hyperleukotrienuria. These factors were aspirin-intolerance, eosinophilic nasal polyposis (ENP), vasculitis, and severe asthma. In ENP there is prominent infiltration of eosinophils in the sinus and polyp tissues, which is linked to adult asthma and aspirin-sensitivity, and ENP is the most important factor for overproduction of CysLTs in asthmatics. We demonstrated that there is a significant decrease in the U-LTE4 concentration after the sinus surgery of asthmatics with and without aspirin intolerance. Recent studies reported that ENP tissue contain and produce a large amount of CysLTs, and there is a close relationship between CysLT production and eosinophil accumulation in ENP. These observations suggest that ENP is not only a local allergic disease, but also a systemic inflammatory disease with CysLT overproduction.