AZITHROMYCIN IMPACT ON NEUTROPHIL OXIDATIVE-METABOLISM DEPENDS ON EXPOSURE TIME

Several antimicrobial agents have already been investigated relating t o their influence on neutrophil ROS generation. Azithromycin provides, a dose-related anti-oxidant effect, after 15 min incubation, with the stimulating agent FMLP, as well with PMA or S. aureus. This finding w as however obtained with concentrations not considered in therapeutics . Since short incubation times are not representative of the physiolog ical situation, and since azithromycin is characterized by prolonged h igh concentrations within phagocytes, the same experiments were perfor med over 2 and 4 h exposures. A time-dependent anti-oxidant effect was then reported. The maximum effect was obtained with PMA (IC50 were 85 6 and 30 mu g/ml for 15 min and 4 h incubation times respectively). Ti me-dependent modifications of neutrophil oxidative metabolism seem to be correlated with intracellular concentrations. Depressed oxidative m etabolism might be related neither to azithromycin cellular toxicity, nor to superoxide scavenging properties. By increasing exposure period s, therapeutic concentrations could therefore lead to an anti-inflamma tory effect, potentially of clinical interest since associated with ba cteriostatic activity.