Effects of azithromycin on ozone-induced airway neutrophilia and cytokine release.
Exposure of humans to ozone causes increased neutrophils and inflammatory cytokines in airway lining fluid. Recent research shows that macrolide antibiotics may reduce interleukin (IL)-8 production by bronchial epithelial cells and inhibit neutrophil chemotaxis. A double-blind, cross-over study was performed in which 12 healthy subjects underwent two separate 4-h exposures to 0.2 parts per million ozone while exercising intermittently. In the 73.5 h before exposure, subjects were pretreated with either 1,250 mg azithromycin or placebo. Sputum induction conducted 74 h pre- and 18 h post-exposure was used to measure total cells, per cent neutrophils, IL-6, and IL-8. There were significant (p<0.05) pre- to post-exposure increases in total cells, neutrophils, IL-6 and IL-8 in both the azithromycin and placebo arms. However, no significant differences were found between azithromycin and placebo conditions in the post- minus pre-exposure value for these variables. The results suggest that in healthy subjects, in the design used, azithromycin, in usual clinical doses, does not have anti-inflammatory effects on human airways as indicated in the measured variables.
Criqui
G I
GI
Lung Biology Center, Dept of Medicine, University of California, San Francisco 94143-0854, USA.
Solomon
C
C
Welch
B S
BS
Ferrando
R E
RE
Boushey
H A
HA
Balmes
J R
JR
D000328:Adult; D000900:Anti-Bacterial Agents; D017963:Azithromycin / Q000494:pharmacology*; D018592:Cross-Over Studies; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D015850:Interleukin-6 / Q000032:analysis / Q000096:biosynthesis*; D016209:Interleukin-8 / Q000032:analysis / Q000096:biosynthesis*; D008168:Lung / Q000502:physiology; D008297:Male; D009504:Neutrophils / Q000187:drug effects*; D010126:Ozone / Q000494:pharmacology*; D009195:Peroxidase / Q000032:analysis / Q000096:biosynthesis*; D013147:Spirometry; D013183:Sputum / Q000737:chemistry* / Q000166:cytology*
D000900:Anti-Bacterial Agents; D015850:Interleukin-6; D016209:Interleukin-8; D010126:Ozone; D017963:Azithromycin; D009195:Peroxidase