The Role of Leukotriene B4 in Allergic Diseases

ABSTRACTLeukotriene B4 (LTB4) is a lipid mediator with potent chemoattractant properties and that is rapidly generated from activated innate immune cells such as neutrophils, macrophages, and mast cells. Elevated levels of LTB4 have been reported in various allergic diseases and these levels have been related to disease activity and response to treatment. Recent studies using LTB4 receptor-1 (BLT1) antagonists or BLT1-deficient mice have revealed that ligation of BLT1 by LTB4 is important for the activation and recruitment of inflammatory cells including neutrophils, eosinophils, monocytes/macrophages, mast cells, dendritic cells, and more recently, effector T cells to inflamed tissues in various inflammatory diseases. The LTB4/BLT1 pathway appears to play an important role in the pathogenesis of severe persistent asthma, aspirin- and exercise-induced asthma, allergic rhinitis, and atopic dermatitis together with other mediators including cysteinyl leukotrienes, cytokines, and chemokines. LTB4 production is in general resistant to corticosteroid treatment. In fact, corticosteroids can upregulate BLT1 expression on corticosteroid-resistant inflammatory cells such as neutrophils, monocytes, and effector memory CD8+ T cells. As a result, this corticosteroid-resistant LTB4/BLT1 pathway may contribute to the development of inflammation in allergic diseases that do not respond to the introduction of corticosteroids. Inhibition of this pathway has potential therapeutic benefit in various allergic diseases that have involvement of corticosteroid-insensitivity