Rhinovirus-induced exacerbations of asthma: How is the β<inf>2</inf>- adrenoceptor implicated?

Rhinovirus (RV) infections are the major cause of asthma exacerbations in children and adults. Under normal circumstances, asthmatic airway obstruction improves spontaneously or characteristically briskly in response to inhaled β2-adrenergic receptor (β2AR) agonists. During virus-associated exacerbations, an impaired response to β2AR agonists is observed; the reason for this is not known. The objective of this study was to determine the effect of RV infection on airway smooth muscle β2AR function. The human cell line Beas-2B and primary human bronchial epithelial cells (HBECs) were infected with RV (multiplicity of infection = 1). After 1 or 5 days for primary and Beas-2B cells, respectively, cell culture supernatants were harvested, UV-irradiated to inactivate RV, and applied to human airway smooth muscle cells for 3 days to assess modifications of β2AR function. RV conditioned medium from Beas-2B and HBECs decreased β2AR agonist-induced cAMP by 50 and 65%, respectively (n = 5; P < 0.05). When cAMP was induced independently of the β2AR using forskolin, no impairment was found. Using flow cytometry, we demonstrated that this decrease was likely the result of β2AR desensitization because membrane but not total cell receptor β2AR was decreased. Pretreatment of HBECs and Beas-2B cells but not human airway smooth muscle cells with the corticosteroids dexamethasone or fluticasone abolished virus-mediated β2AR loss of function. This study shows that epithelial infection with RV induces a decrease of β2AR function on airway smooth muscle cells, potentially explaining the clinical observation of loss of β2AR agonist function during RV-induced asthma exacerbations