Azithromycin modulates neutrophil function and circulating inflammatory mediators in healthy human subjects.
Effects on human neutrophils and circulating inflammatory mediators were studied in 12 volunteers who received azithromycin (500 mg/day, p.o.) for 3 days. Blood was taken 1 h before treatment, 2.5, 24 h and 28 days after the last dose. An initial neutrophil degranulating effect of azithromycin was reflected in rapid decreases in azurophilic granule enzyme activities in cells and corresponding increases in serum. The oxidative response to a particulate stimulus was also acutely enhanced. These actions were associated with high plasma and neutrophil drug concentrations. A continuous fall in chemokine and interleukin-6 serum concentrations, within the non-pathological range, accompanied a delayed down-regulation of the oxidative burst and an increase in apoptosis of neutrophils up to 28 days after the last azithromycin dose. Neutrophils isolated from blood at this time point still contained detectable drug concentrations. Acute neutrophil stimulation could facilitate antibacterial effects of azithromycin, while delayed, potentially anti-inflammatory activity may curtail deleterious inflammation.
PLIVA d.d., Research Division, Prilaz Baruna Filipovića 25 HR-10 000, Zagreb, Croatia.
Ognjen
O
Culić
Vesna
V
Eraković
Ivana
I
Cepelak
Karmela
K
Barisić
Karmen
K
Brajsa
Zeljko
Z
Ferencić
Ruzica
R
Galović
Ines
I
Glojnarić
Zoran
Z
Manojlović
Vesna
V
Munić
Renata
R
Novak-Mircetić
Verica
V
Pavicić-Beljak
Mirna
M
Sucić
Marija
M
Veljaca
Tihana
T
Zanić-Grubisić
Michael J
MJ
Parnham
D000209:Acute-Phase Proteins / Q000032:analysis; D000284:Administration, Oral; D000328:Adult; D000893:Anti-Inflammatory Agents / Q000008:administration & dosage / Q000097:blood / Q000494:pharmacology*; D000975:Antioxidants / Q000378:metabolism; D017209:Apoptosis; D017963:Azithromycin / Q000008:administration & dosage / Q000097:blood / Q000494:pharmacology*; D015815:Cell Adhesion Molecules / Q000097:blood; D018925:Chemokines / Q000097:blood; D016207:Cytokines / Q000097:blood*; D004797:Enzyme-Linked Immunosorbent Assay; D005978:Glutathione / Q000378:metabolism; D005979:Glutathione Peroxidase / Q000378:metabolism; D005980:Glutathione Reductase / Q000378:metabolism; D006801:Humans; D008297:Male; D009504:Neutrophils / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D009566:Nitrates / Q000097:blood; D009573:Nitrites / Q000097:blood; D018384:Oxidative Stress / Q000187:drug effects; D013482:Superoxide Dismutase / Q000378:metabolism
D000209:Acute-Phase Proteins; D000893:Anti-Inflammatory Agents; D000975:Antioxidants; D015815:Cell Adhesion Molecules; D018925:Chemokines; D016207:Cytokines; D009566:Nitrates; D009573:Nitrites; D017963:Azithromycin; D005979:Glutathione Peroxidase; D013482:Superoxide Dismutase; D005980:Glutathione Reductase; D005978:Glutathione