Experimental endotoxemia in humans: analysis of cytokine release and coagulation, fibrinolytic, and complement pathways

摘要: Endotoxemia was evoked by bolus injection of Escherichia coli endotoxin (2 ng/kg body weight) in six healthy subjects to investigate the early kinetics cytokine release relation development clinical and hematologic abnormalities frequently seen gram-negative septicemia. The plasma concentration tumor necrosis factor (TNF) increased markedly after 30 45 minutes, reached a maximal level 60 90 minutes. In each volunteer, initial increase interleukin 6 (IL-6) concentrations occurred 15 minutes TNF increase, IL-6 were at 120 150 A transient temperature pulse rate simultaneously with increases, whereas significant decrease blood pressure These changes proportional concentrations. Coagulation activation, as assessed rise prothrombin fragments thrombin-antithrombin III complexes, noted absence activation contact system. two- sixfold tissue plasminogen activator (t-PA) von Willebrand antigen indicated endothelial cell activation. This started respectively. t-PA coincided fibrinolytic pathway, measured plasmin-alpha 2-antiplasmin complexes. activity subsequently offset inhibitor, observed injection, reaching peak 240 No complement detected. results show that humans induces an early, rapidly counteracted response, more long-lasting thrombin mechanism other than system addition, our data suggest endotoxin-induced leukopenia are mediated TNF.