Cytokine release and adhesion molecule expression by stimulated human bronchial epithelial cells are downregulated by salmeterol.

β2-adrenoreceptor agonists are able to modulate various aspects of airway cell functions involved in the inflammatory and repair processes characterizing a variety of respiratory disorders. Human bronchial epithelial cells (HBECs), which can act as immune effector cells and express β2-adrenoreceptors, were used to test the effects of different concentrations (0.1–100.0nM) of salmeterol (Salm) on adhesion molecule expression and chemokine/cytokine release. HBECs, freshly isolated from resected bronchi at the time of surgery in ex-smokers with lung cancer, constitutively expressed over 3 times more ICAM-1 than VCAM-1 (P<0.05) and secreted greater amounts of IL-8 than of GM-CSF or RANTES (P<0.001). Stimulation of HBECs with IL-4, TNF-α or IL-4 plus TNF-α-upregulated ICAM-1 expression (P<0.05) and increased GM-CSF and IL-8 secretion (P<0.05). Similarly, VCAM-1 expression was significantly increased by IL-4 plus TNF-α, while RANTES release was significantly enhanced by IL-4 or by IL-4 plus TNF-α (P<0.05), but not by TNF-α alone (P>0.05). Dose-response curves showed that Salm, at concentration >1.0nM, was effective in inhibiting adhesion molecule expression and cytokine release by HBECs (P<0.05). At a Salm concentration of 10 nM the degree of inhibition observed was similar for ICAM-1 and VCAM-1 expression (37.2±9.3% and 32.9±9.6%, respectively; P>0.05), but higher for RANTES (88.4±4.4%), as compared to IL-8 (21.8±7.0%) or GM-CSF (30.1±6.6%; P<0.05, each comparison). Thus, adhesion molecules and cytokines may be expressed/released at very different levels by unstimulated or stimulated HBECs and those activities appear to be modulated by Salm.