In vitro resistance to dexamethasone of basophils from patients receiving long-term steroid therapy.
Previous studies have shown that in vitro culture of human basophils for 24 h with physiologic concentrations of glucocorticoids leads to a pronounced inhibition of the subsequent release of histamine or leukotrienes when the cells are challenged with anti-IgE. However, both acute and chronic therapy in vivo with steroids fails to lead to an impairment of subsequent histamine release in vitro. To test whether the failure of in vivo steroid therapy to inhibit subsequent in vitro histamine release was due to the selection of a subpopulation of basophils that responded normally to anti-IgE but were resistant to steroids, the in vitro sensitivity to inhibition of mediator release by steroids in basophils obtained from normal patients as well as patients receiving chronic steroid therapy was studied. Basophils from steroid-dependent asthmatics (SDA) who had been receiving steroid doses orally of 7.5 to 50 mg equivalents of prednisone per day (mean, 19 mg), patients with collagen vascular disease (CVD) who had been receiving steroids orally of 4 to 80 mg equivalents (mean, 25 mg), non-steroid-dependent asthmatics (NSDA), and normal subjects were prepared, and their in vitro response to the potent glucocorticoid, dexamethasone, was determined. Dexamethasone was considerably more effective as an inhibitor of histamine release from basophils of normal subjects and NSDA than from basophils of SDA and patients with CVD. Because this was true in both SDA and patients with CVD, it seems most likely to be the result of the treatment with steroids rather than the underlying disease processes. Such a finding may be the result of a steroid-induced selection process by which sensitive cells are removed from the bloodstream in steroid-treated persons.
Lampl
K L
KL
Lichtenstein
L M
LM
Schleimer
R P
RP
D000328:Adult; D001249:Asthma / Q000188:drug therapy*; D001491:Basophils / Q000187:drug effects* / Q000378:metabolism; D003095:Collagen Diseases / Q000188:drug therapy; D003907:Dexamethasone / Q000494:pharmacology*; D004351:Drug Resistance; D005260:Female; D005938:Glucocorticoids / Q000627:therapeutic use*; D006636:Histamine Release / Q000187:drug effects; D006801:Humans; D007073:Immunoglobulin E / Q000276:immunology; D066298:In Vitro Techniques; D008297:Male; D008875:Middle Aged
D005938:Glucocorticoids; D007073:Immunoglobulin E; D003907:Dexamethasone