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

Curr Allergy Asthma Rep. 2016 Jul;16(7):48. doi: 10.1007/s11882-016-0628-3.

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.

Keywords: Allergic disease; Leukotrienes; Lipids; Platelet-activating factor; Prostanoids; Sphingolipids.

Publication types

  • Research Support, N.I.H., Extramural
  • Review

MeSH terms

  • Animals
  • Eicosanoids / physiology
  • Humans
  • Hypersensitivity / drug therapy
  • Hypersensitivity / immunology
  • Hypersensitivity / metabolism*
  • Immunologic Factors / pharmacology
  • Immunologic Factors / therapeutic use
  • Leukotrienes / physiology
  • Lipid Metabolism
  • Molecular Targeted Therapy
  • Platelet Activating Factor / physiology
  • Signal Transduction
  • Sphingolipids / physiology

Substances

  • Eicosanoids
  • Immunologic Factors
  • Leukotrienes
  • Platelet Activating Factor
  • Sphingolipids