ERYTHROMYCIN MODULATES IL-8 EXPRESSION IN NORMAL AND INFLAMED HUMAN BRONCHIAL EPITHELIAL-CELLS

Erythromycin (EM) and its 14-member macrolide analogues have attracted attention for its effectiveness in a variety of airway diseases, incl uding diffuse panbronchiolitis (DPB), sinobronchial syndrome, and chro nic sinusitis. However, its mechanisms of action remain unelucidated. We evaluated the effects of several antibiotics on IL-8 expression by normal and transformed human bronchial epithelial cells, an important source of this potent chemokine involved in cell recruitment into the airways, EM and clarithromycin (CAM) uniquely suppressed mRNA levels a s well as the release of IL-8 at the therapeutic and noncytotoxic conc entrations (% inhibition of IL-8 protein release: 25.0 +/- 5.67% and 3 7.5 +/- 8.99%, respectively, at 10(-6) M). The other antimicrobes, inc luding a 16-member macrolide josamycin, showed no effect. Bronchial ep ithelial cells from very peripheral airways as well as from main bronc hi were obtained from patients with chronic airway inflammatory diseas es, and EM and CAM inhibited IL-8 release from these cells. Among five patients who underwent bronchoscopy before and after macrolide treatm ent, four showed decreased levels of IL-8 expression in airway epithel ium as assessed by reverse transcription and polymerase chain reaction . Our findings showed these 14-member macrolides had inhibitory effect on IL-8 expression in human bronchial epithelial cells, and this new mode of action may have relevance to their clinical effectiveness in a irway diseases.