THE EFFECTS OF THE POTENT GLUCOCORTICOID BUDESONIDE ON ADHESION OF EOSINOPHILS TO HUMAN VASCULAR ENDOTHELIAL-CELLS AND ON ENDOTHELIAL EXPRESSION OF ADHESION MOLECULES

An important early event in the formation of the allergic late-phase c ellular infiltrate is the adhesion of eosinophils to vascular endothel ium. Because glucocorticoids are potent inhibitors of this late-phase inflammatory reaction, we examined the effect of the glucocorticoid bu desonide on in vitro adhesion of human eosinophils to cultured human u mbilical vein endothelial cells (HUVEC). Pretreatment of eosinophils, HUVEC or both with budesonide (10(-7) M) did not inhibit either baseli ne adhesion or that stimulated by interleukin-1beta (50 U/ml, 4 hr) or interleukin-4 (100 U/ml, 21-23 hr) or the leukocyte activators N-form yl-methionyl-leucyl-phenylalanine (10(-6) M, 10 min) or platelet-activ ating factor (10(-6) M, 10 min). Pretreatment of HUVEC with budesonide also failed to affect expression of the adhesion molecules E-selectin , intercellular adhesion molecule-1, or vascular cell adhesion molecul e-1 on resting HUVEC or after stimulation with interleukin-1beta (10 U /ml, 4 hr), tumor necrosis factor (6 U/ml, 4 hr) or interleukin-4 (50 U/ml, 24 hr). Because budesonide failed to inhibit stimulus-induced eo sinophil adhesion responses or endothelial adhesion molecule expressio n, we speculate that glucocorticoids inhibit the formation of eosinoph il-enriched tissue infiltrates by inhibiting the production rather tha n the activity of eosinophil- or endothelial-activating factors or by altering the survival of eosinophils in tissues.