Strategies for Leukotriene Modulation in Dermatology: Even More Visionary Perspectives? An Update

Giovanni      Luigi Capella

Abstract

In the last decade, substantial progress has been made in the study of eicosanoid autacoids, such as leukotrienes [LTs], which were already known to be heavily involved in inflammatory skin processes. The subject has extended from the detailed description of 5-lipoxygenase cascade products and regulation to the discovery of detailed interrelations among LT physiology and apparently loosely related fields such as peroxisome-proliferating activating receptors (PPARs), pro-resolving mediators, control of fibrosing processes, and nuclear signalling. Many of these advances clearly present aspects which could be relevant to experimental and clinical dermatology. Surprisingly enough, and unfortunately due at least in part to restrictive policies in off-label use of drugs all over the world, the use of available LT modulators in dermatology has remained the same as ten years ago, with the significant but marginal exception of Sjögren-Larsson syndrome. From a dermatological viewpoint, the state of the art is far from desirable. A survey of relevant advances, with special regards to medicinal chemistry topics related to anti-inflammatory intervention is provided, together with visionary proposals for future, substantial improvement in the management of patients suffering from inflammatory skin diseases, in which LT-related pathogenetic and resolving mechanism play so important a role.

Keywords: Leukotriene antagonist, Leukotriene receptor blocking agent, Lipoxygenase inhibitor, Platelet activating factor, Prostaglandin, Lipoxin, Skin diseases, Sjogren-Larsson syndrome, HISTAMINE-RECEPTOR, ANTI-LEUKO-TRIENE BOTANY.