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

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.