Lipid Mediators of Allergic Disease: Pathways, Treatments, and Emerging Therapeutic Targets.

ABSTRACT

Bioactive lipids are critical regulators of inflammation. Over the last 75 years, these diverse compounds have emerged as clinically-relevant mediators of allergic disease pathophysiology. Animal and human studies have demonstrated the importance of lipid mediators in the development of asthma, allergic rhinitis, urticaria, anaphylaxis, atopic dermatitis, and food allergy. Lipids are critical participants in cell signaling events which influence key physiologic (bronchoconstriction) and immune phenomena (degranulation, chemotaxis, sensitization). Lipid-mediated cellular mechanisms including (1) formation of structural support platforms (lipid rafts) for receptor signaling complexes, (2) activation of a diverse family of G-protein coupled receptors, and (3) mediating intracellular signaling cascades by acting as second messengers. Here, we review four classes of bioactive lipids (platelet activating factor, the leukotrienes, the prostanoids, and the sphingolipids) with special emphasis on lipid synthesis pathways and signaling, atopic disease pathology, and the ongoing development of atopy treatments targeting lipid mediator pathways.