The responses of normal and psoriatic skin to single and multiple topical applications of leukotriene B4.

Topical application of single doses of leukotriene B4, (5-500 ng) under occlusion to the skin of normal volunteers and to the clinically normal skin of patients with untreated stable plaque psoriasis caused an inflammatory reaction lasting several days. Histologically, intraepidermal neutrophil microabscesses were seen in both groups following 50 ng applications of leukotriene B4, but there were significantly fewer intraepidermal neutrophils in the psoriatic than in the normal subjects. Nine repeated daily applications of leukotriene B4 (50 ng) to the same site were associated with a reduction of the visible inflammatory response in both volunteer groups, although application of a single 50 ng dose of leukotriene B4 to an adjacent, previously untreated site at the end of the multiple dose experiments elicited acute erythema and edema. Histologically, there were significantly fewer intraepidermal neutrophils in biopsies from sites to which 9 applications of leukotriene B4 were made than in sites to which 1 dose had been applied at the end of the multiple-dose experiments in both psoriatic and normal volunteers. Therefore, repeated application of leukotriene B4 is associated with decreased responsiveness which is due to a local mechanism in the repeatedly treated skin. No subject developed psoriasis following single or multiple applications of leukotriene B4, suggesting that the production of leukotriene B4 in the epidermis is unlikely to be a primary pathogenic event in this disease.