Differential antibiotic-induced endotoxin release and interleukin-6 production by human umbilical vein endothelial cells (HUVECs): amplification of the response by coincubation of HUVECs and blood cells |
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Authors: | M Arditi J Zhou |
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Affiliation: | Division of Infectious Diseases, Childrens Hospital of Los Angeles, University of Southern California School of Medicine, 90027, USA. |
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Abstract: | The activation of human vascular endothelial cells (ECs), as assessed by interleukin (IL)-6 production, was investigated in response to antibiotic-induced lipopolysaccharide release from Escherichia coli. Antibiotic-induced killing of E. coli resulted in the activation of human umbilical vein endothelial cells (HUVECs). Imipenem and meropenem induced faster killing of E. coli than ceftriaxone at 2 and 6 h. However, imipenem-induced bacterial killing resulted in significantly less IL-6 release compared with meropenem or ceftriaxone. When HUVECs were coincubated with diluted (4%) human blood, bacterial killing-induced total IL-6 release was significantly higher than that produced by HUVECs or by 4% blood cells alone. These observations suggest that antibiotic-induced lipopolysaccharide release activates both endothelial cells and monocytes and that the effect is significantly amplified when endothelial cells and monocytes are coincubated. Imipenem, which has a greater affinity for penicillin-binding protein (PBP) 2, induced less IL-6 release from blood and endothelial cells than did PBP 3-specific ceftriaxone and meropenem. |
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