THE ROLE OF LEUKOTRIENES IN INFLAMMATION

Objective: To review the biochemistry and biological activities of leukotrienes, focusing on their role in the mediation of inflammatory diseases. Data Sources: MEDLINE (1966-1994), EMBASE (Excerpta Medica; 1974-1994), and other biomedical and drug directory databases (such as Pharmaprojects and IMSworld R&D Focus [1991-1994]) were searched to identify English-language articles (basic science, clinical trial research, and review articles) and abstracts of conference proceedings on leukotrienes and related terms. Study Selection: Basic science studies on leukotrienes and clinical research studies on the use of leukotriene inhibitors and antagonists in the treatment of inflammatory diseases such as asthma, psoriasis, rheumatoid arthritis, and ulcerative colitis. Data Extraction: Detailed summaries of data from basic science studies on the formation and actions of leukotrienes and from clinical studies of drugs that block the synthesis or receptor-mediated actions of leukotrienes. Data Synthesis: Leukotrienes are biologically active 5-lipoxygenase products of arachidonic acid metabolism that are involved in the mediation of various inflammatory disorders. Of these, leukotriene B-4 (a potent chemoattractant for leukocytes) and the sulfidopeptide leukotrienes C-4, D-4, and E(4) (which increase vascular permeability and constrict smooth muscle) exert their biological actions through specific ligand-receptor interactions. Selective leukotriene inhibitors and receptor antagonists are currently under evaluation in the treatment of Various inflammatory diseases. Conclusions: Further data on the in vitro and in vivo activities of the leukotriene inhibitors and antagonists should clarify the role of leukotrienes in the pathogenesis of such inflammatory diseases as asthma, rheumatoid arthritis, and inflammatory bowel disease. Leukotriene inhibitors and antagonists will probably become important agents in the group of anti-inflammatory drugs.