Function of human alveolar macrophages after a 3-day course of azithromycin in healthy volunteers.
Azithromycin (AZM) is a new macrolide antibiotic with a high intracellular/extracellular concentration ratio. Immunomodulatory and antiinflammatory properties have been reported with other macrolides, especially erythromycin. The aim of the present study was to evaluate the effect of AZM on the production of proinflammatory mediators by alveolar macrophages (AM) up to 4 weeks after a 3-day course of AZM (500 mg, once a day). Nineteen non-smoking healthy male subjects were investigated with bronchoscopy and bronchoalveolar lavage. Group 1 received no treatment. Groups 2, 3, and 4 were bronchoscoped 1, 7 and 30 days, respectively, after AZM administration. AZM concentrations were simultaneously measured in plasma and in AM extracts. In serum, AZM levels were higher in group 2 (32.8 +/- 14.2 micrograms/l), at the lower limit of detection in group 3 (2.8 +/- 1.7 micrograms/l), and no longer detectable in group 4. In AM extracts, the highest concentrations were measured in group 2 (51.6 +/- 28.3 ng/microliter) and in group 3 (31.8 +/- 17.2 ng/microliter), and were detected up to 30 days after treatment in group 4 (2.9 +/- 2.3 ng/microliter). There was no significant differences between groups for blood or BAL proinflammatory cytokines levels (TNF-alpha, IL-1 beta, IL-6), and for superoxide generation by AM. We conclude that a 3-day course of AZM 500 mg/day in healthy subjects does not alter the proinflammatory cytokine profile in blood and in AM despite the prolonged tissue impregnation by this drug.
Aubert
J D
JD
Départment de Médecine, CHUV, Université de Lausanne, Switzerland. John-David.Aubert@chuv.hospvd.ch
Juillerat-Jeanneret
L
L
Fioroni
P
P
Dayer
P
P
Plan
P A
PA
Leuenberger
P
P
D000293:Adolescent; D000328:Adult; D000900:Anti-Bacterial Agents / Q000097:blood / Q000378:metabolism / Q000494:pharmacology*; D017963:Azithromycin / Q000097:blood / Q000378:metabolism / Q000494:pharmacology*; D018893:Bronchoalveolar Lavage; D001999:Bronchoscopy; D016207:Cytokines / Q000187:drug effects / Q000378:metabolism; D006801:Humans; D016676:Macrophages, Alveolar / Q000187:drug effects* / Q000502:physiology; D008297:Male; D012016:Reference Values; D013481:Superoxides / Q000378:metabolism
D000900:Anti-Bacterial Agents; D016207:Cytokines; D013481:Superoxides; D017963:Azithromycin