Proinflammatory effects of erythromycin, clarithromycin and azithromycin on human endothelial cells in vitro
Abstract number: 1732_275
Millrose M., Baumann-Wilschke I., Webb J., Stahlmann R.
An inflammatory reaction of the venous vessel is a common clinical problem that is observed after intravenous application of antibiotics and other drugs. The local irritation of the endothelium at the site of infusion leads to an inflammatory response with an increased expression of various cell surface antigens. Among these are CD 34, E-Selectin (CD 62E), ICAM-1 (CD 54) and VCAM-1 (CD 106). We studied the effects of three closely related antibiotics on human endothelial cells in vitro. We used the endothelial cell line EA.hy 926 and analysed the reaction by means of flow cytometry (FACScan, Becton Dickinson). Cells were incubated with clarithromycin or azithromycin at concentrations ranging from 100 mg/l to 800 mg/l and at concentrations ranging from 200 mg/l to 1400 mg/l for erythromycin. Such concentrations occur under therapeutic conditions at the site of infusion. Subsequently, they were stained with fluoresceinisothiocyanate- or phycoerythrin-conjugated monoclonal IgG mouse-antibodies for the four antigens mentioned above. Cells were incubated with the drugs for 2 h and analysis was carried out after an additional time period of 22 h. In control cells, we found positively stained cells at the following levels: CD 34 (2%), E-Selectin (4%), ICAM-1 (14%) and VCAM-1 (2%). The most pronounced changes were observed at 800 mg/l (erythromycin), 600 mg/l (azithroymcin), and 400 mg/l (clarithromycin). Erythromycin (800 mg/l) caused significantly increased expressions of all epitopes [CD 34 (+6%), E-Selectin (+5%), ICAM-1 (+15%) and VCAM-1 (+5%)]. At 600 mg/l the azalide azithromycin provokes a stronger upregulation of the proinflammatory antigens: CD 34 (+17%), E-Selectin (+16%), ICAM-1 (+27%) and VCAM-1 (+17%). Clarithromycin at a concentration of 400 mg/l causes a similar effect as erythromycin at twice this concentration [CD 34 (+6%), E-Selectin (+7%), ICAM-1 (+23%) and VCAM-1 (+4%)]. Analysis of the cell surface markers involved in cell-cell-interactions proved to be a useful approach to further study the mechanism of infusion phlebitis and to compare the proinflammatory effects of related compounds in vitro.
|Session name:||European Society of Clinical Microbiology and Infectious Diseases|
|Location:||ICC, Munich, Germany|
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