Strategies for Leukotriene Modulation in Dermatology: Current Evidence and Visionary Perspectives

Leukotrienes (LTs) are a complex family of eicosatetrenoic acid derivatives containing a conjugated triene chain first isolated from leukocytes. The biosynthesis of LTs can be started, or completed, or fully performed at various degrees in several mammal cells including mastocytes, basophils, eosinophils, neutrophils, macrophages, endothelial cells, erythrocytes, and platelets. LTs are potent proinflammatory autacoids: as a whole, their actions include plasma extravasation and induction of edema, leukocyte aggregation, smooth muscle contraction, and polymorphonuclear chemoattraction. Several molecules interfering with the synthesis of LTs mediated by the enzyme 5-lipo-oxygenase or its activating protein (FLAP), or with the binding of LTs to specific receptors have been developed in recent years, mainly for the treatment of bronchial asthma. Three such molecules (LT biosynthesis inhibitor; zileuton; LT receptor antagonists; zafirlukast, and montelukast) are currently marketed worldwide. Owing to the ubiquitous distribution of LTs in the organism, and their involvement in a host of inflammatory disorders, it has become clear that these drugs can be useful in the treatment of many conditions, other than asthma. In the dermatological domain, LT-modulating drugs (either commercially available ones or experimental agents) have been shown to be active or promising in several conditions such as atopic dermatitis, urticaria (chronic idiopathic, pressure delayed, cold- or aspirin-induced), and psoriasis. Further research, clinical, and practical implications, as well as visionary perspectives are surveyed and discussed.