title: The in vitro effects of quinupristin/dalfopristin, erythromycin and levofloxacin at low concentrations on the expression of different cell adhesion molecules on the surface of endothelial cells (Eahy926).
abstract: OBJECTIVE
  Infusion phlebitis is a common clinical problem associated with some antimicrobial agents. The pathomechanism of infusion phlebitis has not yet been elucidated, however, it has been proposed that chemical irritation of the endothelium leads to subsequent sterile inflammation with recruitment and migration of leukocytes. In the present study, cultured endothelial cells were exposed to antibiotics at clinically relevant concentrations to detect changes in various cell surface markers.
  
  
  METHODS
  Cells from the endothelial hybrid cell line Eahy926 were exposed to quinupristin/dalfopristin, erythromycin and levofloxacin at increasing concentrations (3, 10, 30 and 100 mg/l) for 24 h. After washing, the cells were marked with monoclonal antibodies against different cell surface antigens (intercellular cell adhesion molecule-1 [ICAM-1], platelet-endothelial cell adhesion molecule-1 [PECAM-1], vascular cell adhesion molecule-1 [VCAM-1], E-selectin, L-selectin, CD34, alpha(2), alpha(5), beta(1) and beta(4) integrin chains and analysed by flow cytometry. For comparison, cells were either untreated or incubated with tumor necrosis factor alpha (TNF-alpha) at a concentration of 10 ng/ml and analysed for ICAM-1, VCAM-1 and E-selectin expression.
  
  
  RESULTS
  There was an increase in ICAM-1 expression on endothelial cells with increasing concentrations of quinupristin/dalfopristin. VCAM-1, E-selectin, L-selectin and CD34 showed an excursive upregulation at the concentration of 100 mg/l only, while no consistent changes were observed for PECAM-1 and the integrins. Markedly less prominent changes in the expression of these adhesion molecules were seen with erythromycin while no relevant changes at all occurred with levofloxacin. The absolute change in ICAM-1 activation with quinupristin/dalfopristin at 100 mg/l (34.4%) was less pronounced than that observed after stimulation with TNF-alpha (>80%).
  
  
  CONCLUSIONS
  The results of this study indicate that antibiotics with a high potential for local cytotoxicity may cause an inflammatory response by endothelial cells even at rather low concentrations. The increase in expression of cell surface markers involved in cell-cell interaction could be an important mechanism in the development of infusion phlebitis.
authors.affiliation: Institute of Clinical Pharmacology and Toxicology, Charité Campus Benjamin Franklin, Garystr. 5, 14195 Berlin, Germany.
authors.forename: Bülent
authors.initials: B
authors.lastname: Kilic
authors.forename: Matthias
authors.initials: M
authors.lastname: Kruse
authors.forename: Ralf
authors.initials: R
authors.lastname: Stahlmann
mesh_terms: D000900:Anti-Bacterial Agents / Q000009:adverse effects*; D015815:Cell Adhesion Molecules / Q000096:biosynthesis* / Q000276:immunology; D002460:Cell Line; D004305:Dose-Response Relationship, Drug; D042783:Endothelial Cells / Q000187:drug effects* / Q000276:immunology / Q000378:metabolism; D004917:Erythromycin / Q000009:adverse effects; D005434:Flow Cytometry; D006801:Humans; D064704:Levofloxacin; D015242:Ofloxacin / Q000009:adverse effects; D010689:Phlebitis / Q000139:chemically induced / Q000276:immunology / Q000378:metabolism; D014769:Virginiamycin / Q000009:adverse effects
chemical_list: D000900:Anti-Bacterial Agents; D015815:Cell Adhesion Molecules; D014769:Virginiamycin; C062940:quinupristin-dalfopristin; D004917:Erythromycin; D064704:Levofloxacin; D015242:Ofloxacin