Cutaneous responses to 12-hydroxy-5,8,10,14-eicosatetraenoic acid (12-HETE)

The responses to 12-HETE in normal human skin have been investigated by means of intradermal and topical administration in 15 subjects. Intradermal infusion of 12-HETE produced a neutrophil polymorphonuclear and mononuclear infiltrate in the dermis. Topical administration resulted in a dose-related erythematous response to 200 ng-50 micrograms. This was accompanied by a neutrophil and mononuclear dermal infiltrate at 6 and 24 h after application. In addition, collections of neutrophils were present in the epidermis in 4 of 10 subjects biopsied at 6 h and in all patients biopsied 24 h after topical application. Intradermal and topical application of 9-hydroxyoctadecadienoic acid (9-HODD), a chemically similar but chemokinetically inactive substance, did not produce neutrophil infiltration of the epidermis, nor did the chemical irritant nonanoic acid. The results suggest that the cellular infiltrates produced in vivo in humans by 12-HETE are due to its chemoattractant properties and are not the result of a nonspecific inflammatory response.