Effects of chronic intracutaneous administration of arachidonic acid and its metabolites. Induction of leukocytoclastic vasculitis by leukotriene B4 and 12-hydroxyeicosatetraenoic acid and its prevention by prostaglandin E2.
Despite the postulated role of arachidonic acid-derived metabolites in the pathophysiology of chronic inflammatory dermatoses such as psoriasis and atopic or contact dermatitis, the cutaneous effects of their chronic application have not yet been investigated. We therefore studied systematically the effects of chronic intracutaneous administration of arachidonic acid, prostaglandin E2 (PGE2), leukotriene B4 (LTB4), and 12-hydroxyeicosatetraenoic acid (12-HETE) in guinea pigs, and describe previously unrecognized findings partly different from those reported in the past for short-term or topical application of these inflammatory mediators. Leukotriene B4 and 12-HETE led to massive histologic changes characteristic of leukocytoclastic vasculitis. These changes could be prevented by concomitant PGE2 administration. In epidermis, LTB4 and 12-HETE caused some spongiosis as well as hyperplasia and increased tritiated thymidine autoradiographic labeling index. Arachidonic acid and PGE2 alone had little effect. These data suggest that in addition to other inflammatory or hyperproliferative dermatoses, arachidonic acid metabolites formed via lipoxygenase pathways could play a major role in leukocytoclastic vasculitis, whereas PGs could exert a tissue-protective effect.
D019377:12-Hydroxy-5,8,10,14-eicosatetraenoic Acid; D000818:Animals; D016718:Arachidonic Acid; D001095:Arachidonic Acids / Q000008:administration & dosage / Q000378:metabolism / Q000494:pharmacology*; D015232:Dinoprostone; D004817:Epidermis / Q000187:drug effects / Q000473:pathology; D005260:Female; D006168:Guinea Pigs; D006893:Hydroxyeicosatetraenoic Acids / Q000037:antagonists & inhibitors / Q000633:toxicity*; D007249:Inflammation; D007267:Injections; D007975:Leukotriene B4 / Q000037:antagonists & inhibitors / Q000633:toxicity*; D011458:Prostaglandins E / Q000494:pharmacology*; D012867:Skin / Q000187:drug effects* / Q000473:pathology; D014657:Vasculitis / Q000139:chemically induced* / Q000473:pathology
D001095:Arachidonic Acids; D006893:Hydroxyeicosatetraenoic Acids; D011458:Prostaglandins E; D007975:Leukotriene B4; D016718:Arachidonic Acid; D019377:12-Hydroxy-5,8,10,14-eicosatetraenoic Acid; D015232:Dinoprostone