title: Macrolide antibiotics broadly and distinctively inhibit cytokine and chemokine production by COPD sputum cells in vitro.
abstract: Macrolide antibiotics are known to exert anti-inflammatory actions in vivo, including certain effects in COPD patients. In order to investigate the immunomodulatory profile of activity of macrolide antibiotics, we have studied the effects of azithromycin, clarithromycin, erythromycin and roxithromycin on the in vitro production of a panel of inflammatory mediators from cells isolated from human, steroid-naïve, COPD sputum samples. Macrolide effects were compared to three other commonly used anti-inflammatory compounds, the corticosteroid dexamethasone, the PDE4 inhibitor, roflumilast and the p38 kinase inhibitor, SB203580. Three of the four tested macrolides, azithromycin, clarithromycin and roxithromycin, exhibited pronounced, concentration-related reduction of IL-1β, IL-6, IL-10, TNF-α, CCL3, CCL5, CCL20, CCL22, CXCL1, CXCL5, and G-CSF release. Further slight inhibitory effects on IL-1α, CXCL8, GM-CSF, and PAI-1 production were also observed. Erythromycin was very weakly active. Qualitatively and quantitatively, macrolides exerted distinctive and, compared to other tested classes of compounds, more pronounced immunomodulatory effects, particularly in terms of chemokine (CCL3, CCL5, CCL20, CCL22, and CXCL5), IL-1β, G-CSF and PAI-1 release. The described modulation of inflammatory mediators could potentially contribute to further definition of biomarkers of macrolide anti-inflammatory activity in COPD.
authors.affiliation: GlaxoSmithKline Research Centre Zagreb Limited, Zagreb, Croatia. nikola.marjanovic@glpg.com
authors.forename: Nikola
authors.initials: N
authors.lastname: Marjanović
authors.forename: Martina
authors.initials: M
authors.lastname: Bosnar
authors.forename: Francesca
authors.initials: F
authors.lastname: Michielin
authors.forename: David R
authors.initials: DR
authors.lastname: Willé
authors.forename: Tatjana
authors.initials: T
authors.lastname: Anić-Milić
authors.forename: Ognjen
authors.initials: O
authors.lastname: Culić
authors.forename: Sanja
authors.initials: S
authors.lastname: Popović-Grle
authors.forename: Mile
authors.initials: M
authors.lastname: Bogdan
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Parnham
authors.forename: Vesna
authors.initials: V
authors.lastname: Eraković Haber
mesh_terms: D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D017963:Azithromycin / Q000494:pharmacology; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D018925:Chemokines / Q000276:immunology*; D017291:Clarithromycin / Q000494:pharmacology; D016207:Cytokines / Q000276:immunology*; D004917:Erythromycin / Q000494:pharmacology; D006801:Humans; D018942:Macrolides / Q000494:pharmacology*; D029424:Pulmonary Disease, Chronic Obstructive / Q000188:drug therapy* / Q000276:immunology; D015575:Roxithromycin / Q000494:pharmacology; D013183:Sputum / Q000166:cytology* / Q000276:immunology
chemical_list: D000900:Anti-Bacterial Agents; D018925:Chemokines; D016207:Cytokines; D018942:Macrolides; D015575:Roxithromycin; D004917:Erythromycin; D017963:Azithromycin; D017291:Clarithromycin