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 micrograms/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 10(3), control 1.8 +/- 0.3 cpm x 10(3), 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-gamma (IFN-gamma), tumor necrosis factor-alpha (TNF-alpha), interleukin (IL)-1 beta and IL-2 (p < 0.001, each comparison). Salmeterol (10(-7) M) or dexamethasone (10(-9) M) induced a similar, statistically significant, downregulation of GM-CSF release (p < 0.05, each comparison) and induced a slight, not significant, decrease in the production of IFN-gamma, TNF-alpha, IL-1 beta 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-alpha, IL-1 beta and IL-2 (p < 0.05, each comparison) but not of IFN-gamma (p > 0.05). Thus beta 2-adrenoceptors may enhance the inhibitory activity of low doses of corticosteroids on allergen-induced BMC activation.
Divisione di Pneumologia, Istituto G. Gaslini, Genova, Italy.
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Silvestri
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D000318:Adrenergic beta-Agonists / Q000494:pharmacology*; D000328:Adult; D000420:Albuterol / Q000031:analogs & derivatives* / Q000494:pharmacology; D000485:Allergens; D002455:Cell Division; D002478:Cells, Cultured; D016207:Cytokines / Q000378:metabolism*; D003907:Dexamethasone / Q000494:pharmacology*; D004357:Drug Synergism; D005260:Female; D005938:Glucocorticoids / Q000494:pharmacology*; D006801:Humans; D007963:Leukocytes, Mononuclear / Q000187:drug effects* / Q000276:immunology; D008297:Male; D000068299:Salmeterol Xinafoate
D000318:Adrenergic beta-Agonists; D000485:Allergens; D016207:Cytokines; D005938:Glucocorticoids; D000068299:Salmeterol Xinafoate; D003907:Dexamethasone; D000420:Albuterol