Azithromycin modulates neutrophil function and circulating inflammatory mediators in healthy human subjects

• Published in: European journal of pharmacology Vol. 450; no. 3; pp. 277 - 289
• Main Authors: Čulić, Ognjen, Eraković, Vesna, Čepelak, Ivana, Barišić, Karmela, Brajša, Karmen, Ferenčić, Željko, Galović, Ružica, Glojnarić, Ines, Manojlović, Zoran, Munić, Vesna, Novak-Mirčetić, Renata, Pavičić-Beljak, Verica, Sučić, Mirna, Veljača, Marija, Žanić-Grubišić, Tihana, Parnham, Michael J
• Format: Journal Article
• Language: English
• Published: Amsterdam Elsevier B.V 30.08.2002; Elsevier
• Subjects: Acute-Phase Proteins - analysis; Administration, Oral; Adult; Anti-Inflammatory Agents - administration & dosage; Anti-Inflammatory Agents - blood; Anti-Inflammatory Agents - pharmacology; Antibacterial agents; Antibiotics. Antiinfectious agents. Antiparasitic agents; Antioxidants - metabolism; Apoptosis; Azithromycin; Azithromycin - administration & dosage; Azithromycin - blood; Azithromycin - pharmacology; Biological and medical sciences; Bones, joints and connective tissue. Antiinflammatory agents; Cell Adhesion Molecules - blood; Chemokines - blood; Cytokine; Cytokines - blood; Degranulation; Enzyme-Linked Immunosorbent Assay; Glutathione - metabolism; Glutathione Peroxidase - metabolism; Glutathione Reductase - metabolism; Human volunteer; Humans; Male; Medical sciences; Neutrophil; Neutrophils - cytology; Neutrophils - drug effects; Neutrophils - metabolism; Nitrates - blood; Nitrites - blood; Oxidative burst; Oxidative Stress - drug effects; Pharmacology. Drug treatments; Superoxide Dismutase - metabolism; Degranulation; Neutrophil; Human volunteer; Azithromycin; Oxidative burst; Cytokine; Human; Oxidative stress; Healthy subject; Antiinflammatory agent; Oral administration; Inflammation; Oxidant; Macrolide; Antibiotic; Cell death; Inflammatory cell; Antibacterial agent; Mechanism of action; Apoptosis
• DOI: 10.1016/S0014-2999(02)02042-3
• ISSN: 0014-2999

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.