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

Background: Long-term administration of macrolide antibiotic substances 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. Methods: Contractile responses of human isolated bronchial strips to electrical field stimulation (EFS) and acetylcholine were assessed under isometric conditions in the absence and presence of erythromycin, roxithromycin, or clarithromycin. Results: Incubation of tissues with erythromycin (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 +/- SE; p < 0.001). In contrast, contractile responses to acetylcholine were not changed. Erythromycin reduced the EFS-induced contraction in a concentration-dependent fashion; the maximal decrease from the baseline response was 92.8% +/- 3.6% (p < 0.001). This inhibitory effect was not altered by propranolol, indomethacin, ouabain, charybdotoxin, or mechanical removal of the epithelium. Roxithromycin and clarithromycin likewise inhibited neurally mediated contraction. Conclusions: These results suggest that macrolides may inhibit cholinergic neuroeffector transmission in the human airway smooth muscle, probably by reducing exocytotic release of acetylcholine from the nerve terminals.