Azithromycin impact on neutrophil oxidative metabolism depends on exposure time.
Several antimicrobial agents have already been investigated relating to 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 was however obtained with concentrations not considered in therapeutics. Since short incubation times are not representative of the physiological situation, and since azithromycin is characterized by prolonged high concentrations within phagocytes, the same experiments were performed over 2 and 4 h exposures. A time-dependent anti-oxidant effect was then reported. The maximum effect was obtained with PMA (IC50 were 856 and 30 micrograms/ml for 15 min and 4 h incubation times respectively). Time-dependent modifications of neutrophil oxidative metabolism seem to be correlated with intracellular concentrations. Depressed oxidative metabolism might be related neither to azithromycin cellular toxicity, nor to superoxide scavenging properties. By increasing exposure periods, therapeutic concentrations could therefore lead to an anti-inflammatory effect, potentially of clinical interest since associated with bacteriostatic activity.
Levert
H
H
Laboratoire de Pharmacologie et Pharmacie Clinique, Faculté des Sciences Pharmaceutiques et Biologiques, Lille, France.
Gressier
B
B
Moutard
I
I
Brunet
C
C
Dine
T
T
Luyckx
M
M
Cazin
M
M
Cazin
J C
JC
D000900:Anti-Bacterial Agents / Q000008:administration & dosage / Q000494:pharmacology*; D000975:Antioxidants / Q000008:administration & dosage / Q000494:pharmacology*; D017963:Azithromycin / Q000008:administration & dosage / Q000494:pharmacology*; D002474:Cell-Free System; D004305:Dose-Response Relationship, Drug; D006801:Humans; D066298:In Vitro Techniques; D007700:Kinetics; D007770:L-Lactate Dehydrogenase / Q000378:metabolism; D009240:N-Formylmethionine Leucyl-Phenylalanine / Q000494:pharmacology; D009504:Neutrophils / Q000187:drug effects* / Q000276:immunology / Q000378:metabolism*; D010587:Phagocytosis; D017382:Reactive Oxygen Species / Q000378:metabolism; D013211:Staphylococcus aureus / Q000276:immunology; D013481:Superoxides / Q000378:metabolism; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology
D000900:Anti-Bacterial Agents; D000975:Antioxidants; D017382:Reactive Oxygen Species; D013481:Superoxides; D009240:N-Formylmethionine Leucyl-Phenylalanine; D017963:Azithromycin; D007770:L-Lactate Dehydrogenase; D013755:Tetradecanoylphorbol Acetate