Effects of Inhaled Fluticasone Propionate and Oral Prednisolone on Lymphocyte β₂-Adrenoceptor Function in Asthmatic Patients

¹ From the Department of Clinical Pharmacology, Ninewells Hospital and Medical School, University of Dundee, Scotland

The aim of the study was to evaluate the facilitatory effects of inhaled corticosteroid on in vitro parameters of lymphocyte β₂-adrenoceptor function in asthmatic patients. Serum cortisol level was also evaluated as a measure of systemic bioactivity. Ten (four female) asthmatic subjects were evaluated, mean (SEM) age was 28.6(2.0) years, and FEV₁ was 79.9%(8.7) predicted. Single doses of inhaled placebo (PL), fluticasone propionate, 1,000 µg (F1000), fluticasone propionate, 2,000 µg(F2000), or oral prednisolone, 50 mg(PRED), were given at 10 PM the previous night and measurements were made 10 h later. Values for β₂-receptor density (logBmax: fmol/10⁶cells) were significantly (p<0.05) greater than PL with PRED but not with inhaled fluticasone (as means and 95% confidence interval [CI] for difference vs PL): PL, 0.27; F1000, 0.30; F2000, 0.32; and PRED, 0.48 (95% CI vs PL, 0.075 to 0.341). Maximal cyclic adenosine monophosphate (cAMP) responses to isoproterenol hydrochloride (isoprenaline (Emax; pmol/10⁶cells) mirrored those for Bmax: PL, 4.00; F1000, 4.68; F2000, 4.26; and PRED, 7.46 (95% CI vs PL, 0.01 to 6.91). Receptor affinity (Kd) was not significantly altered by any treatment. There was significant (p<0.05) suppression of serum cortisol (nmol/L) with F2000 and PRED compared with PL: PL, 307.9; F1000, 323.2; F2000, 130.1 (95% CI vs PL, 69.76 to 285.8) and PRED, 51.8 (95% CI vs PL, 144.11 to 368.01). Thus, high-dose inhaled fluticasone propionate did not have any facilitatory effects on lymphocyte β₂-adrenoceptor parameters as compared with oral prednisolone which upregulated β₂-receptor density and increased cAMP response. In contrast, high-dose inhaled fluticasone (2,000 µg) significantly suppressed serum cortisol. In conclusion, there would appear to be a dissociation in systemic sensitivity between effects of inhaled corticosteroid on adrenal suppression and lymphocyte β₂-adrenoceptor regulation.

Key Words: asthma • β₂-adrenoceptor • inhaled fluticasone • prednisolone

Submitted on June 16, 1995
Accepted on August 10, 2007

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