J Asthma Allergy Clin Immunol.  2000 Dec;20(6):927-935.

The binding affinity of glucocorticoid receptor in the peripheral blood mononuclear cells from patients with steroid-resistant and steroid-responsive asthma

Affiliations
  • 1Department of Internal Medicine, Ewha Womans, University College of Medicine, Seoul, Korea.
  • 2Department of Pharmacology, Ewha Womans, University College of Medicine, Seoul, Korea.

Abstract

BACKGROUND
Glucocorticoids (GC) are the most potent medications used to control airway inflammation associated with asthma. The aim of this study was to see whether alterations in GC receptor binding contribute to poor response to GC therapy in severe asthma.
METHODS
Seventeen patients with severe persistent bronchial asthma were studied. Patients were classified as GC sensitive if their morning FEV1 increased >15% after a 1-week course of systemic GC (>prednisolone 40mg/day) and GC-resistant if they failed to increase >15%. GC receptor binding affinity for dexamethasone of peripheral blood mononuclear cells (PBMCs) were determined by using a radioligand binding assay and Scatchard analysis.
RESULTS
There were no significant differences of age, serum IgE levels, peripheral blood eosinophils and atopic states between GC-resistant (n=10) and GC-responsive (n=7) groups. GC-resistant patients had significantly decreased GC receptor binding affinity (Kd=24.3+/-9.55) compared to the GC sensitive patients (Kd=13.5+/-1.48) and normal controls (n=6, Kd=4.24+/-1.09).
CONCLUSION
These data suggest that decreased binding affinity of GC receptor is an important factor in clinical GC resistance in chronic severe asthma.

Keyword

Glucocorticoid receptor; steroid resistant asthma; steroid responsive asthma

MeSH Terms

Asthma*
Dexamethasone
Eosinophils
Glucocorticoids
Humans
Immunoglobulin E
Inflammation
Receptors, Glucocorticoid*
Dexamethasone
Glucocorticoids
Immunoglobulin E
Receptors, Glucocorticoid
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