title: Effect of macrolide antibiotics on human endothelial cells activated by Chlamydia pneumoniae infection and tumor necrosis factor-alpha.
abstract: This study investigated the potential anti-inflammatory activity of 3 macrolide antibiotics, clarithromycin, roxithromycin, and azithromycin, in an in vitro model of transendothelial migration (TEM). Human umbilical vein endothelial cells (HUVECs) were seeded in Transwell inserts, treated with serial dilutions of the antibiotics, and infected with Chlamydia pneumoniae or stimulated with tumor necrosis factor (TNF)-alpha. In HUVECs infected with C. pneumoniae or stimulated with TNF-alpha, both azithromycin and roxithromycin caused significant decreases in neutrophil and monocyte TEM, compared with antibiotic-free controls. Clarithromycin had no detectable effect in either group. Azithromycin caused significant decreases in interleukin (IL)-8 and monocyte chemotactic protein (MCP)-1, whereas roxithromycin significantly decreased IL-8. This study indicates heterogeneity in the anti-inflammatory activity of these antibiotics. Mechanisms of monocyte and neutrophil TEM inhibition by azithromycin and roxithromycin are unclear but may be partially due to inhibition of IL-8 and MCP-1 production.
authors.affiliation: Division of Infectious Diseases, Department of Medicine, University of Louisville School of Medicine, 500 S. Preston Street, Louisville, KY 40292, USA. silviauriarte@yahoo.com
authors.forename: Silvia M
authors.initials: SM
authors.lastname: Uriarte
authors.forename: Robert E
authors.initials: RE
authors.lastname: Molestina
authors.forename: Richard D
authors.initials: RD
authors.lastname: Miller
authors.forename: Jorge
authors.initials: J
authors.lastname: Bernabo
authors.forename: Alicia
authors.initials: A
authors.lastname: Farinati
authors.forename: Kumiko
authors.initials: K
authors.lastname: Eiguchi
authors.forename: Julio A
authors.initials: JA
authors.lastname: Ramirez
authors.forename: James T
authors.initials: JT
authors.lastname: Summersgill
mesh_terms: D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D002465:Cell Movement / Q000187:drug effects*; D002478:Cells, Cultured; D018932:Chemokine CCL2 / Q000378:metabolism; D023521:Chlamydophila Infections / Q000382:microbiology; D016993:Chlamydophila pneumoniae / Q000502:physiology*; D004730:Endothelium, Vascular / Q000166:cytology / Q000187:drug effects / Q000382:microbiology*; D006801:Humans; D016209:Interleukin-8 / Q000378:metabolism; D018942:Macrolides; D009000:Monocytes / Q000502:physiology*; D009504:Neutrophils / Q000502:physiology*; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology
chemical_list: D000900:Anti-Bacterial Agents; D018932:Chemokine CCL2; D016209:Interleukin-8; D018942:Macrolides; D014409:Tumor Necrosis Factor-alpha