Influence of salmeterol, a long-acting beta 2-adrenoceptor agonist, on IgE-mediated histamine release from human...

Salmeterol, a long-acting beta 2-adrenoceptor agonist, prevents early and late asthmatic responses in atopic asthmatics and inhibits the release of inflammatory mediators from various cells and tissues. We investigated the effect of salmeterol on in vitro basophil histamine release (BHR). Washed basophil leukocytes from allergic (n = 6) and nonallergic subjects (n = 18) were preincubated for 10 min with different concentrations of salmeterol prior to stimulation with antigens (Ag) and anti-IgE for 45 min. BHR was detected by an automated fluorometric assay. If control BHR (without inhibition) reached > or = 30% of the total histamine content, maximal % inhibition (Imax, mean +/- SEM) and the concentration of salmeterol causing 30% inhibition (IC30, geometric mean) were calculated. At concentrations of between 1 and 100 microM salmeterol, concentration-dependent inhibition of release was found for Ag- and anti-IgE-mediated BHR. The Imax of anti-IgE-mediated BHR reached 46 +/- 16% at 30 microM salmeterol. IC30 values were 12 microM for Ag- and 8 microM for anti-IgE-induced BHR. Higher concentrations of salmeterol induced BHR in all subjects (n = 24, 100 microM: 28 +/- 5% BHR), overlapping the inhibitory effect on BHR. Kinetic studies using 30 microM salmeterol (n = 10) showed > 30% inhibition with short preincubation periods (< 10 s). Salbutamol, an older, widely used beta 2-adrenoceptor agonist, had no effect on IgE-mediated BHR (n = 8). We conclude that salmeterol significantly inhibits IgE-mediated histamine release from human leukocytes in the micromolar range.