Selective inhibition of the cutaneous late but not immediate allergic response 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 misoprostol on allergen-induced cutaneous immediate- and late-phase allergic reactions 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 micrograms) or placebo and then had skin testing on 2 different days. The immediate- and late-phase skin response was monitored for 6 h. Skin biopsy was obtained from 5 selected donors at 5 h. In vitro studies included the effect of misoprostol on eosinophil chemotaxis, eosinophil survival, basophil histamine release, and cytokine production by lymphocytes. All subjects developed an immediate wheal reaction and a late-phase induration in response to dust mite allergens after taking placebo. Misoprostol selectively inhibited the late- but not the immediate-phase response (p < 0.05). Histologic studies revealed a trend toward a reduced number of inflammatory cells in the skin dermis after misoprostol treatment. Misoprostol significantly (p < 0.05) inhibited eosinophil chemotaxis and the production of granulocyte-macrophage colony-stimulating factor by lymphocytes at concentrations > or = 10(-8) M. However, at significantly lower concentrations (> or = 10(-12) M) misoprostol blocked cytokine-stimulated eosinophil survival. Thus, misoprostol has potent antiallergic effects and blocks the cutaneous late-phase allergic inflammation.
Alam
R
R
Department of Internal Medicine, University of Texas Medical Branch, Galveston 77550.
Dejarnatt
A
A
Stafford
S
S
Forsythe
P A
PA
Kumar
D
D
Grant
J A
JA
D000328:Adult; D000818:Animals; D001707:Biopsy, Needle; D002634:Chemotaxis, Leukocyte / Q000187:drug effects / Q000276:immunology; D003864:Depression, Chemical; D004311:Double-Blind Method; D004391:Dust; D004804:Eosinophils / Q000187:drug effects / Q000276:immunology; D005260:Female; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000037:antagonists & inhibitors; D006801:Humans; D006968:Hypersensitivity, Delayed / Q000188:drug therapy* / Q000276:immunology / Q000473:pathology; D006969:Hypersensitivity, Immediate / Q000188:drug therapy* / Q000276:immunology / Q000473:pathology; D008297:Male; D008875:Middle Aged; D016595:Misoprostol / Q000627:therapeutic use*; D008925:Mites / Q000276:immunology; D012867:Skin / Q000187:drug effects* / Q000276:immunology / Q000473:pathology; D012882:Skin Tests / Q000379:methods
D004391:Dust; D016595:Misoprostol; D016178:Granulocyte-Macrophage Colony-Stimulating Factor