title: Thrombomodulin release in baboon sepsis: its dependence on the dose of Escherichia coli and the presence of tumor necrosis factor.
abstract: This study was designed to test whether thrombomodulin is shed in septic baboons and whether shedding is blocked by antibody to tumor necrosis factor (anti-TNF). Live Escherichia coli were injected intravenously into 24 baboons according to one of the following regimens: 5 x 10(8) or 2 x 10(9) cfu/kg (n = 6/8), 2 x 10(9) cfu/kg with placebo (n = 5), or pretreatment with 1 mg/kg anti-TNF 2 h before E. coli injection (n = 5). E. coli administration resulted in a significant release of thrombomodulin in a dose-dependent manner; however, thrombomodulin release was significantly attenuated (180 to 40 ng/mL) by anti-TNF pretreatment. This is parallel to the reduction of neutrophil activation (elastase). These results provide evidence for an E. coli dose-related and TNF-dependent thrombomodulin release into the plasma of septic baboons and suggest a possible role of anti-TNF in protection of the endothelium.
authors.affiliation: Ludwig Boltzmann Institute for Experimental and Clinical Traumatology, Vienna, Austria.
authors.forename: H
authors.initials: H
authors.lastname: Redl
authors.forename: G
authors.initials: G
authors.lastname: Schlag
authors.forename: A
authors.initials: A
authors.lastname: Schiesser
authors.forename: J
authors.initials: J
authors.lastname: Davies
mesh_terms: D000410:Alanine Transaminase / Q000097:blood; D000818:Animals; D004926:Escherichia coli; D008297:Male; D010196:Pancreatic Elastase / Q000097:blood; D010215:Papio; D017395:Plasminogen Activator Inhibitor 1 / Q000378:metabolism; D010976:Platelet Count; D018805:Sepsis / Q000378:metabolism*; D018180:Thrombomodulin / Q000378:metabolism*; D014409:Tumor Necrosis Factor-alpha / Q000502:physiology*
chemical_list: D017395:Plasminogen Activator Inhibitor 1; D018180:Thrombomodulin; D014409:Tumor Necrosis Factor-alpha; D000410:Alanine Transaminase; D010196:Pancreatic Elastase