Inhibition of immunoglobulin, but not polypeptide base-stimulated release of histamine and arachidonic acid by anti-inflammatory steroids

Abstract

Incubation overnight of purified rat mast cells with glucocorticoids inhibited the release of histamine and [1-14C]arachidonic acid (and its metabolites) stimulated by three immunoglobulin (Ig) E-like secretagogues, anti-IgE, the antigen-ovalbumin and concanavalin A. In contrast, pretreatment with glucocorticoids did not affect either histamine or [1-14C]arachidonic acid release stimulated by somatostatin, compound 48/80 or the calcium ionophore A23187. Glucocorticoids inhibited IgE-like arachidonic acid and histamine release with an order of potency similar to their in vivo anti-inflammatory potencies (i.e., fluocinolone greater than dexamethasone greater than hydrocortisone greater than cortisone). This inhibition required several hours and was temperature-dependent, suggesting a specific glucocorticoid receptor mechanism. IgE-stimulated Ca++ influx was decreased by hydrocortisone pretreatment. These results suggest that glucocorticoids specifically uncouple IgE-mediated calcium flux with subsequent inhibition of histamine and arachidonic acid release.