title: Effects of fluoroquinolones on the migration of human phagocytes through Chlamydia pneumoniae-infected and tumor necrosis factor alpha-stimulated endothelial cells.
abstract: The anti-inflammatory activities of three quinolones, levofloxacin, moxifloxacin, and gatifloxacin, were investigated with an in vitro model of transendothelial migration (TEM). Human umbilical vein endothelial cells (HUVEC) were seeded in Transwell inserts, treated with serial dilutions of antibiotics, infected with Chlamydia pneumoniae, or stimulated with tumor necrosis factor alpha (TNF-alpha). Neutrophils or monocytes were also preincubated with serial dilutions of each antibiotic. TEM was assessed by light microscopic examination of the underside of the polycarbonate membrane, and levels of interleukin-8 (IL-8) and monocyte chemotactic protein 1 (MCP-1) were measured by enzyme-linked immunosorbent assay. In HUVEC infected with C. pneumoniae or stimulated with TNF-alpha, all fluoroquinolones significantly decreased neutrophil and monocyte TEM, compared to antibiotic-free controls. Moxifloxacin and gatifloxacin produced a significant decrease in IL-8 in C. pneumoniae-infected and TNF-alpha-stimulated HUVEC; however, moxifloxacin was the only fluoroquinolone that produced a significant decrease in MCP-1 levels under both conditions. Results from this study indicate similarities in the anti-inflammatory activities of these fluoroquinolones, although no statistically significant decrease in chemokine secretion was observed when levofloxacin was used. Mechanisms of neutrophil and monocyte TEM inhibition by fluoroquinolone antibiotics are unknown but may be partially due to inhibition of IL-8 and MCP-1 production, respectively.
authors.affiliation: Infectious Diseases Laboratory, Room 311, Instructional Building, 500 South Preston St., University of Louisville, Louisville, KY 40292, USA.
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: D000890:Anti-Infective Agents / Q000494:pharmacology*; D001372:Aza Compounds / Q000494:pharmacology; D002465:Cell Movement / Q000187:drug effects; D018925:Chemokines / Q000096:biosynthesis; D002689:Chlamydia; D042783:Endothelial Cells / Q000166:cytology* / Q000187:drug effects; D024841:Fluoroquinolones / Q000494:pharmacology*; D000077734:Gatifloxacin; D006801:Humans; D064704:Levofloxacin; D009000:Monocytes / Q000187:drug effects; D000077266:Moxifloxacin; D009504:Neutrophils / Q000187:drug effects; D015242:Ofloxacin / Q000494:pharmacology; D010586:Phagocytes / Q000187:drug effects*; D018410:Pneumonia, Bacterial / Q000473:pathology*; D011804:Quinolines / Q000494:pharmacology; D013268:Stimulation, Chemical; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology*; D014471:Umbilical Veins / Q000166:cytology / Q000473:pathology
chemical_list: D000890:Anti-Infective Agents; D001372:Aza Compounds; D018925:Chemokines; D024841:Fluoroquinolones; D011804:Quinolines; D014409:Tumor Necrosis Factor-alpha; D064704:Levofloxacin; D015242:Ofloxacin; D000077734:Gatifloxacin; D000077266:Moxifloxacin