EFFECTS OF INHALED FLUTICASONE PROPIONATE AND ORAL PREDNISOLONE ON LYMPHOCYTE BETA(2)-ADRENOCEPTOR FUNCTION IN ASTHMATIC-PATIENTS

The aim of the study was to evaluate the facilitatory effects of inhal ed corticosteroid on in vitro parameters of lymphocyte beta(2)-adrenoc eptor function in asthmatic patients. Serum cortisol level was also ev aluated as a measure of systemic bioactivity. Ten (four female) asthma tic subjects were evaluated, mean (SEM) age was 28.6(2.0) years, and F EV(1) was 79.9%(8.7) predicted. Single doses of inhaled placebo (PL), fluticasone propionate, 1,000 mu g (F1000), fluticasone propionate, 2, 000 mu g(F2000), or oral prednisolone, 50 mg(PRED), were given at 10 P M the previous night and measurements were made 10 h later. Values for beta(2)-receptor density (logBmax: fmol/10(6)cells) were significantl y (p<0.05) greater than PL with PRED but not with inhaled fluticasone (as means and 95% confidence interval [CI] for difference vs FL): FL, 0.27; F1000, 0.30; F2000, 0.32; and PRED, 0.48 (95% CI vs FL, 0.075 to 0.341). Maximal cyclic adenosine monophosphate (cAMP) responses to is oproterenol hydrochloride (isoprenaline (Emax; pmol/10(6)cells) mirror ed those for Bmax: FL, 4.00; F1000, 4.68; F2000, 4.26; and PRED, 7.46 (95% CI vs FL, -0.01 to 6.91). Receptor affinity (Kd) was not signific antly altered by any treatment. There was significant (p<0.05) suppres sion of serum cortisol (nmol/L) with F2000 and PRED compared with FL: FL, 307.9; F1000, 323.2; F2000, 130.1 (95% CI vs FL, 69.76 to 285.8) a nd PRED, 51.8 (95% CI vs FL, 144.11 to 368.01). Thus, high-dose inhale d fluticasone propionate did not have any facilitatory effects on lymp hocyte beta(2)-adrenoceptor parameters as compared with oral prednisol one which upregulated beta(2)-receptor density and increased cAMP resp onse. In contrast, high-dose inhaled fluticasone (2,000 mu g) signific antly suppressed serum cortisol. In conclusion, there would appear to be a dissociation in systemic sensitivity between effects of inhaled c orticosteroid on adrenal suppression and lymphocyte beta(2)-adrenocept or regulation.