Differential effects of anti-cytokine treatment on bronchoalveolar hemostasis in endotoxemic chimpanzees

American Journal of Respiratory and Critical Care Medicine
M LeviJ W ten Cate

Abstract

Activation and inhibition of coagulation and fibrinolysis was analyzed in bronchoalveolar lavage (BAL) fluids obtained from endotoxin-challenged chimpanzees. The mediatory role of tumor necrosis factor-alpha (TNF-alpha) and interleukin-6 (IL-6) on endotoxin-induced changes in bronchoalveolar coagulation and fibrinolysis was investigated in experiments in which the infusion of endotoxin was combined with the administration of monoclonal anti-TNF-alpha or anti-IL-6 antibodies. Endotoxin infusion elicited a marked increase in bronchoalveolar thrombin generation as measured by levels of prothrombin activation fragment F1+2 and thrombin-antithrombin complexes. Markers for intrinsic pathway activation were not detectable, suggesting that the thrombin generation was mediated by the tissue factor-dependent route. Levels of antithrombin were low before the injection of endotoxin and not detectable hereafter. The administration of anti-IL-6 antibody completely abolished the endotoxin-induced activation of bronchoalveolar coagulation, whereas treatment with anti-TNF-alpha antibody only partly inhibited this effect. Bronchoalveolar fibrinolytic activity, due to urokinase-type plasminogen activator (u-PA), was significantly depressed after ...Continue Reading

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Citations

Apr 12, 2003·Critical Care Medicine·Wolfram Ruf, Matthias Riewald
Apr 12, 2003·Critical Care Medicine·Marcel LeviTom van der Poll
Apr 12, 2003·Critical Care Medicine·Pierre-François LaterreJean-François Dhainaut
Dec 6, 2001·American Journal of Respiratory and Critical Care Medicine·K E Welty-WolfC A Piantadosi
Dec 23, 2006·Critical Care : the Official Journal of the Critical Care Forum·Lars HesletPär I Johansson
Jan 1, 2010·Mediterranean Journal of Hematology and Infectious Diseases·Nicola SemeraroMario Colucci
Oct 22, 2008·Microvascular Research·James H Finigan
Feb 18, 2009·European Journal of Haematology·Laurens NieuwenhuizenDouwe H Biesma
Nov 2, 2012·Journal of Thrombosis and Haemostasis : JTH·G J GlasM Levi
Aug 26, 2006·Veterinary Immunology and Immunopathology·T R Scott, H S Lillehoj
Aug 16, 2005·American Journal of Physiology. Lung Cellular and Molecular Physiology·Karen E Welty-WolfClaude A Piantadosi
Jul 5, 2006·The Journal of Immunology : Official Journal of the American Association of Immunologists·Rosemarijn RenckensTom van der Poll
Jan 16, 2019·Lab Animal·Lingye ChenBryan D Kraft
Jul 23, 2021·Klinicheskaia laboratornaia diagnostika·A N AripovM R Khidoyatova

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