Taniguchi Masami, Higashi Noritaka, Ono Emiko, Mita Haruhisa, Akiyama Kazuo
Clinical Research Center, National Hospital Organization, Sagamihara National Hospital, Kanagawa, Japan.
Allergol Int. 2008 Dec;57(4):313-20. doi: 10.2332/allergolint.08-RAI-0040. Epub 2008 Nov 1.
Cysteinyl leukotrienes (CysLTs: leukotrienes C(4), D(4), and E(4)) have long been implicated in the pathogenesis of asthma and several allergic diseases. LTE(4) has been identified as a major metabolite of LTC(4), and urinary LTE(4) (U-LTE(4)) is considered as the most reliable analytic parameter for monitoring the endogenous synthesis of CysLTs. From recent studies on the U-LTE(4) associated with adult stable asthma we identified four factors for hyperleukotrieneuria, namely, 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 the overproduction of CysLTs in asthmatics. We also demonstrated that anaphylaxis and eosinophilic pneumonia (EP) are associated with a marked increase in the U-LTE(4) concentration. Under these disease conditions, U-LTE(4) may be one of the candidate biomarkers. Moreover, the changes in U-LTE(4) concentrations may provide valuable information concerning therapeutic targets.
半胱氨酰白三烯(CysLTs:白三烯C4、D4和E4)长期以来一直被认为与哮喘及多种过敏性疾病的发病机制有关。白三烯E4(LTE4)已被确定为白三烯C4(LTC4)的主要代谢产物,尿LTE4(U-LTE4)被视为监测CysLTs内源性合成的最可靠分析参数。通过近期对与成人稳定期哮喘相关的U-LTE4的研究,我们确定了高白三烯尿症的四个因素,即阿司匹林不耐受、嗜酸性粒细胞性鼻息肉病(ENP)、血管炎和重度哮喘。在ENP中,鼻窦和息肉组织中有显著的嗜酸性粒细胞浸润,这与成人哮喘和阿司匹林敏感性有关,且ENP是哮喘患者中CysLTs产生过多的最重要因素。我们还证明,过敏反应和嗜酸性粒细胞性肺炎(EP)与U-LTE4浓度的显著升高有关。在这些疾病状态下,U-LTE4可能是候选生物标志物之一。此外,U-LTE4浓度的变化可能为治疗靶点提供有价值的信息。