Eikosanoids

Eicosanoids, sometimes spelled eikosanoids, are a family of bioactive lipid mediators derived from polyunsaturated fatty acids with 20 carbon atoms, most notably arachidonic acid. They are produced on demand when cell membranes are stimulated, following release of arachidonic acid by phospholipase A2. The fatty acid is then oxidized by cyclooxygenases (COX), lipoxygenases (LOX), or cytochrome P450 enzymes to generate several classes of compounds: prostaglandins and thromboxanes via COX; leukotrienes and lipoxins via LOX; and epoxyeicosatrienoic acids (EETs) via P450 pathways. Other oxidation products may include specialized prostaglandins derived from EPA or DGLA.

Physiologically, eicosanoids function as local mediators with paracrine or autocrine actions and act through specific receptors, commonly G-protein–coupled receptors. Prostaglandins regulate inflammation, pain, fever, vascular tone, and glandular secretions; thromboxanes promote platelet aggregation and vasoconstriction; prostacyclin (PGI2) inhibits platelet aggregation and causes vasodilation; leukotrienes contribute to bronchoconstriction, vascular permeability, and chemotaxis in allergic and inflammatory responses; lipoxins generally promote resolution of inflammation; EETs influence vascular tone, renal function, and anti-inflammatory signaling.

Clinical relevance: nonsteroidal anti-inflammatory drugs (NSAIDs) inhibit COX enzymes, reducing prostaglandin synthesis and pain and inflammation; aspirin irreversibly acetylates COX-1/COX-2. Leukotriene receptor antagonists are used for asthma and allergic rhinitis. Prostacyclin analogs are used to treat pulmonary arterial hypertension. Modulation of eicosanoid pathways is a therapeutic target in inflammatory diseases, cardiovascular disorders, and some cancers. Eicosanoids are short-lived and rapidly metabolized, limiting their systemic exposure.

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