Section Review: Pulmonary-Allergy, Dermatological, Gastrointestinal & Arthritis: Leukotriene B4receptor antagonists: Recent clinical developments

Abstract

his brief review concentrates on the latest developments involving the application of leukotriene B4 (LTB4) receptor antagonists to the treatment of inflammation, with special emphasis on early clinical results. Since last reviewed [1], a select number of LTB4 antagonists have become the subject of Phase I/II studies designed to demonstrate oral bioavailability and pharmacologic efficacy. The role of this dihydroxy fatty acid, derived from arachidonic acid via the 5-lipoxygenase pathway, in the initiation and progression of inflammation, has been discussed at length [2]. Most of the biological functions of LTB4 are ascribed to its activation and recruitment of inflammatory cells, particularly neutrophils, in nanomolar concentrations via a receptor mechanism. It has been postulated that reduction of LTB4 levels in man could palliate the symptoms associated with inflammatory conditions as diverse as rheumatoid arthritis, inflammatory bowel disease (IBD), and asthma [3]. Zileuton, which reduces levels of both LTB4 and the cysteinyl leukotrienes via inhibition of 5-lipoxygenase, has already shown good clinical efficacy in the treatment of aspirin-induced asthma, but was less effective in IBD [4]. As a novel anti-inflammatory therapy, treatment with an LTB4 receptor antagonist may provide a useful alternative to current intervention centring on administration of cyclo-oxygenase inhibitors and steroids.