INHIBITORY EFFECT OF GLUCOCORTICOSTEROIDS ON ANTI-IGE-INDUCED HISTAMINE-RELEASE FROM HUMAN BASOPHILIC LEUKOCYTES - EVIDENCE FOR A DUAL MECHANISM OF ACTION

Anti-IgE-induced histamine release from human leukocytes is inhibited when the cells before challenge are cultured overnight in the presence of glucocorticoids (GCS). GCS might exert their effect by at least a dual mechanism of action. Histamine release was induced by a suboptimum concentration of anti-IgE. When the release recorded in the presence of the steroid is plotted against the release recorded in its absence, the data points of several experiments fit a regression line characterized by 2 parameters: its slope and its intercept with the abscissa. Structure-activity examination with selected GCS indicates that the orders of potency for affecting these 2 parameters are not identical. Pulse experiments suggest that the cells require different times of contact with the steroid to express inhibition according to the 2 parameters. The removal of adherent cells or platelets did not markedly affect the degree of leukocyte histamine release or its inhibition by a given GCS, suggesting that the steroid interacts directly with the basophil. Steroid-induced inhibition was not affected by the putative phospholipase A2-inhibitor p-bromophenacylbromide (BPB) or the 5-lipoxygenase inhibitor nordihydroguaiaretic acid (NDGA).