Salmeterol enhances the inhibitory activity of dexamethasone on allergen-induced blood mononuclear cell activation

The possibility that salmeterol could interfere with the inhibitory effect of glucocorticosteroids on allergen-induced activation of leukocytes was assessed in cultures of human blood mononuclear cells (BMCs). BMCs, recovered from 27 patients (21 ± 4 years of age) sensitized to Dermatophagoides pteronyssinus (Der p), were incubated with a purified Der p extract (10 μg/ml) for 7 days in the presence of salmeterol (10^-8 and 10^-7 M) and/or dexamethasone (10^-10 and 10^-9 M). BMC proliferation and cytokine release were respectively tested by [³H]thymidine incorporation and EASIA. Stimulation with Der p extract induced a significant BMC proliferation (Der p 18.7 ± 1.9 cpm x 10³, control 1.8 ± 0.3 cpm x 10³, p <0.01) which was significantly inhibited both by salmeterol and dexamethasone (p <0.05, each comparison). The inhibition of BMC proliferation induced by dexamethasone (10^-9 M) was significantly enhanced by salmeterol 10^-7 M (p <0.05). Evaluation of cytokine levels in BMC supernatants showed that Der p extract significantly increased the release of granulocyte-macrophage colony-stimulating factor (GM-CSF), interferon-γ (IFN-γ), tumor necrosis factor-α (TNF-α), interleukin (IL)-1β and IL-2 (p <0.001, each comparison). Salmeterol (10^-7 M) or dexamethasone (10^-9 M) induced a similar, statistically significant, downregulation of GMCSF release (p <0.05, each comparison) and induced a slight, not significant, decrease in the production of IFN-γ, TNF-α, IL-1β and IL-2 (p > 0.05, each comparison). Interestingly, salmeterol (10^-7 M) significantly enhanced the inhibitory activity of dexamethasone (10^-9 M) on the release of GM-CSF, TNF-α, IL-1β and IL-2 (p <0.05, each comparison) but not of IFN-γ (p > 0.05). Thus β₂-adrenoceptors may enhance the inhibitory activity of low doses of corticosteroids on allergen-induced BMC activation.