Section Review: Pulmonary-Allergy, Dermatological, Gastrointestinal & Arthritis: Leukotriene B₄ receptor antagonists: Recent clinical developments

Abstract

This 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.