SELECTIVE-INHIBITION OF THE CUTANEOUS LATE BUT NOT IMMEDIATE ALLERGICRESPONSE TO ANTIGENS BY MISOPROSTOL, A PGE ANALOG - RESULTS OF A DOUBLE-BLIND, PLACEBO-CONTROLLED RANDOMIZED STUDY

The objective of this study was to investigate the effect of misoprost ol on allergen-induced cutaneous immediate- and late-phase allergic re actions in a double-blind placebo-controlled randomized study. We also studied the mechanism of antiallergic effects of misoprostol. A total of 16 dust mite-allergic patients received misoprostol (200 mug) or p lacebo and then had skin testing on 2 different days. The immediate- a nd late-phase skin response was monitored for 6 h. Skin biopsy was obt ained from 5 selected donors at 5 h. In vitro studies included the eff ect of misoprostol on eosinophil chemotaxis, eosinophil survival, baso phil histamine release, and cytokine production by lymphocytes. All su bjects developed an immediate wheal reaction and a late-phase indurati on in response to dust mite allergens after taking placebo. Misoprosto l selectively inhibited the late- but not the immediate-phase response (p < 0.05). Histologic studies revealed a trend toward a reduced numb er of inflammatory cells in the skin dermis after misoprostol treatmen t. Misoprostol significantly (p < 0.05) inhibited eosinophil chemotaxi s and the production of granulocyte-macrophage colony-stimulating fact or by lymphocytes at concentrations greater-than-or-equal-to 10(-8) M. However, at significantly lower concentrations (greater-than-or-equal -to 10(-12) M) misoprostol blocked cytokine-stimulated eosinophil surv ival. Thus, misoprostol has potent antiallergic effects and blocks the cutaneous late-phase allergic inflammation.