EFFECTS OF MACROLIDE ANTIBIOTICS ON NEURALLY-MEDIATED CONTRACTION OF HUMAN ISOLATED BRONCHUS

Background: Long-term administration of macrolide antibiotic substance s is an alternative therapy used in the treatment of asthma and airway hyperresponsiveness, but neither its mechanism of action nor whether this substance exerts an immediate action in the airways is known. Met hods: Contractile responses of human isolated bronchial strips to elec trical field stimulation (EFS) and acetylcholine were assessed under i sometric conditions in the absence and presence of erythromycin, roxit hromycin, or clarithromycin. Results: Incubation of tissues with eryth romycin (3 X 10(-5) mol/L) attenuated the contractile responses to EFS so that the stimulus frequency required to produce 50% of the maximal contraction increased form 4.1 +/- 0.5 to 10.1 +/- 0.7 Hz (mean +/- S E; p < 0.001). In contrast, contractile responses to acetylcholine wer e not changed. Erythromycin reduced the EFS-induced contraction in a c oncentration-dependent fashion; the maximal decrease from the baseline response was 92.8% +/- 3.6% (p < 0.001). This inhibitory effect was n ot altered by propranolol, indomethacin, ouabain, charybdotoxin, or me chanical removal of the epithelium. Roxithromycin and clarithromycin l ikewise inhibited neurally mediated contraction. Conclusions: These re sults suggest that macrolides may inhibit cholinergic neuroeffector tr ansmission in the human airway smooth muscle, probably by reducing exo cytotic release of acetylcholine from the nerve terminals.