Cyclic AMP-induced inhibition of IgE-mediated hypersensitivity in human skin.

The effect of drugs that increase the cellular concentration of cyclic AMP on antigen-evoked histamine release from IgE sensitized human skin was studied. Using a new model consisting of human skin slices passively sensitized by antigen-specific IgE antibody, histamine release following challenge of skin by antigen was consistently inhibited by adrenalin and theophylline in a dose-related manner. That the inhibitory effect of adrenalin is due to β-adrenergic stimulation was established using the specific β-adrenergic antagonist propranolol. When adrenalin and theophylline were combined marked synergism was demonstrated. Further confirmation of these results was obtained using dibutyryl cyclic AMP which produced dose-related inhibition of antigen-evoked histamine release from human skin. These results demonstrate that drugs that increase cellular cyclic AMP consistently inhibit human cutaneous anaphylaxis and raise the possibility that cyclic AMP exerts a regulatory effect on IgE-mediated hypersensitivity in human skin.