Inhibition of Cutaneous Hypersensitivity by Cyclic AMP

Abstract

The effect of drugs which increase the cellular concentration of cyclic AMP on IgE-mediated cutaneous hypersensitivity reactions in skin was studied using skin from ovalbumin-sensitised rats. Theophylline, which reduces degradation of cyclic AMP, caused inhibition of antigen-induced histamine release. Synergism was demonstrated when adrenaline in a concentration which was not itself inhibitory caused marked enhancement of theophylline inhibition. The pure β-adrenergic agent isoprenaline produced inhibition in extremely low concentrations. Direct evidence of an inhibitory role for cyclic AMP was obtained using dibutyryl cyclic AMP which produced a dose-related inhibition of histamine release from skin. This evidence should lead to trials of β-adrenergic drugs and xanthines in the treatment of immediate hypersensitivity reactions in human skin.