EFFECTS OF GLUCOCORTICOIDS AND BETA-ADRENOCEPTOR AGONISTS ON THE PROLIFERATION OF AIRWAY SMOOTH-MUSCLE

An increase in airway smooth muscle is a characteristic feature of ast hma. Because beta-adrenoceptor agonists and corticosteroids are common ly used in the treatment of asthma we have studied the effects of thes e medicines on the growth of airway smooth muscle. These agents were i ncubated with bovine airway smooth muscle cells for 40 h for measureme nt of thymidine incorporation and 64 h for measurement of cell counts. Salbutamol inhibited thymidine incorporation (IC50 = 60 nM) and led t o a reduction in cell number (IC50 = 10 nM). At 10 mu M there was a 14 .6 +/- 2.6% reduction in cell number. Salmeterol also inhibited the gr owth of the airway smooth muscle cells but the effect did not plateau at 10 mu M. At this concentration there was an 89.5 +/- 3.6% reduction in thymidine incorporation and a 44.1 +/- 5.2% reduction in cell numb er. Cortisol and beclomethasone dipropionate were more potent than sal butamol in inhibiting thymidine incorporation with IC50 values of 5 nM and 0.2 nM respectively. Cortisol 100 nM led to a 16.6 +/- 6.5% reduc tion and beclomethasone dipropionate 3 nM led to a 17.8 +/- 5.8% reduc tion in cell number. If similar effects occur in man and in vivo, thes e medicines could act directly on airway smooth muscle to inhibit the development of hyperplasia.