Prostaglandins, leukotrienes, and hydroxy fatty acids in epidermis

Abstract

The skin is an organ that displays a highly active metabolism of polyunsaturated fatty acids (PUFA). Deficiency of the 18 carbon (n-6) dietary PUFA (linoleic acid) in epidermis results in scaly dermatoses and disruption of the skin barrier system. The skin possesses the enzyme systems to metabolize and interconvert a variety of lipids. For instance, it metabolizes arachidonic acid (an n-6 PUFA) via the cyclooxygenase pathway into cyclic products, predominantly prostaglandin E2 and prostaglandin F2 alpha. These prostaglandins modulate normal physiological processes at low physiological concentrations. However, at high concentrations, such as result from UV irradiation, they elicit inflammatory reactions. The skin can also metabolize 18-carbon and 20-carbon PUFA (n-6) via the 12- and 15-lipoxygenase pathways to produce predominantly monohydroxy fatty acids: 13-hydroxyoctadecadienoic acid (13-HODE), 12-hydroxyeicosatetraenoic acid (12-HETE), 15-hydroxyeicosatetraenoic acid (15-HETrE), and 15-hydroxyeicosatetraenoic acid (15-HETE). The latter two have potent anti-inflammatory properties. Therefore, it seems possible that elevation of these HETEs in vivo via dietary or topical means could suppress the cutaneous inflammatory reactions elicited by excessive generation of prostaglandins and leukotrienes. Thus, the supplementation of diets with appropriate purified vegetable oil and/or fish oil may serve as a less toxic monotherapy or as an adjunct to standard regimens in the management of skin inflammatory disorders.