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.
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.
Arditi
M
M
Division of Infectious Diseases, Childrens Hospital of Los Angeles, University of Southern California School of Medicine, 90027, USA.
Zhou
J
J
D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D001773:Blood Cells / Q000502:physiology*; D002443:Ceftriaxone / Q000494:pharmacology; D002450:Cell Communication; D002478:Cells, Cultured; D004730:Endothelium, Vascular / Q000187:drug effects / Q000276:immunology*; D004731:Endotoxins / Q000378:metabolism* / Q000494:pharmacology; D004926:Escherichia coli / Q000187:drug effects*; D006801:Humans; D015378:Imipenem / Q000494:pharmacology; D015850:Interleukin-6 / Q000096:biosynthesis*; D007700:Kinetics; D000077731:Meropenem; D013845:Thienamycins / Q000494:pharmacology; D014471:Umbilical Veins
D000900:Anti-Bacterial Agents; D004731:Endotoxins; D015850:Interleukin-6; D013845:Thienamycins; D015378:Imipenem; D002443:Ceftriaxone; D000077731:Meropenem