MODULATION OF EICOSANOID FORMATION BY LESIONAL SKIN OF PSORIASIS - ANEX-VIVO SKIN MODEL

The purpose of the present study was to develop an ex vivo skin model to determine the capacity of lesional skin of psoriasis to form leukot riene B4 and other eicosanoids. Keratomed skin samples were incubated in the presence of the calcium ionophore A23187 and arachidonic acid f or 45 min at 37-degrees-C. After extraction of lipids, eicosanoids wer e determined by quantitative reversed-phase high-performance liquid ch romatography in combination with specific radioimmunoassays. We found that stimulation of skin samples with A23187 and arachidonic acid incr eased the amount of leukotriene B4 4.0-fold. The 12-lipoxygenase produ ct, 12-hydroxy-eicosatetraenoic acid, and the 15-lipoxygenase product, 15-hydroxy-eicosatetraenoic acid, were both increased 2.7-fold. The c yclooxygenase product, prostaglandin E2, was increased 8.0-fold. Simil ar incubations using psoriatic scales did not result in formation of e icosanoids. Incubations with the 5-lipoxygenase inhibitor RS43179 inhi bited the formation of leukotriene B4 and prostaglandin E2 without sig nificantly affecting the formation of 12-hydroxy-eicosatetraenoic acid and 15-hydroxy-eicosatetraenoic acid. These results reveal that lesio nal psoriatic skin ex vivo has the enzymatic capacity to increase the levels of eicosanoids. This provides an ex vivo skin model to determin e whether putative lipoxygenase inhibitors are able to modulate the fo rmation of eicosanoids in psoriatic skin.