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.
Culić
Ognjen
O
PLIVA d.d., Research Division, Prilaz Baruna Filipovića 25 HR-10 000, Zagreb, Croatia.
Eraković
Vesna
V
Cepelak
Ivana
I
Barisić
Karmela
K
Brajsa
Karmen
K
Ferencić
Zeljko
Z
Galović
Ruzica
R
Glojnarić
Ines
I
Manojlović
Zoran
Z
Munić
Vesna
V
Novak-Mircetić
Renata
R
Pavicić-Beljak
Verica
V
Sucić
Mirna
M
Veljaca
Marija
M
Zanić-Grubisić
Tihana
T
Parnham
Michael J
MJ
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