Arachidonic acid derivatives as mediators of asthma

Arachidonic acid metabolites generated by the cyclooxygenase pathway and by the various lipoxygenase pathways are produced by both resident pulmonary cells and infiltrating cells from the vascular compartment. The various proinflammatory biologic activities of these naturally occurring compounds include bronchoconstriction, increased vascular permeability, alterations in vasomotor tone, enhanced mucus secretion, and granulocyte adherence and chemotaxis. The leukotrienes derived from the 5-lipoxygenase pathway are particularly potent as mediators of inflammation, requiring only nanomolar concentrations for the evocation of their effects. Thus, although a variety of potent cyclooxygenase inhibitors are currently available for anti-inflammatory therapy, therapeutic modalities for the downregulation of leukotriene biosynthesis or efficacy would be highly desirable. Current concepts about the enzymatic cascade in leukotriene generation, the prospects for dietary modification as an adjunct to pharmacotherapeutic intervention, and the implications of specific receptors in leukotriene-mediated events are therefore considered.