|
|
 Previous Article | Table of Contents | Next Article 
Experimental endotoxemia in humans: analysis of cytokine release and
coagulation, fibrinolytic, and complement pathways
SJ van Deventer, HR Buller, JW ten Cate, LA Aarden, CE Hack and A Sturk
Department of Hematology, Academic Medical Center, Amsterdam, The
Netherlands.
Endotoxemia was evoked by bolus injection of Escherichia coli endotoxin (2
ng/kg body weight) in six healthy subjects to investigate the early
kinetics of cytokine release in relation to the development of clinical and
hematologic abnormalities frequently seen in gram-negative septicemia. The
plasma concentration of tumor necrosis factor (TNF) increased markedly
after 30 to 45 minutes, and reached a maximal level after 60 to 90 minutes.
In each volunteer, the initial increase of plasma interleukin 6 (IL-6)
concentrations occurred 15 minutes after the initial TNF increase, and
maximal IL-6 concentrations were reached at 120 to 150 minutes. A transient
increase in body temperature and pulse rate occurred simultaneously with
the initial TNF and IL-6 increases, whereas a significant decrease in blood
pressure occurred after 120 minutes. These changes were proportional to the
changes in TNF and IL-6 concentrations. Coagulation activation, as assessed
by a rise of prothrombin fragments and thrombin-antithrombin III complexes,
was noted after 120 minutes, in the absence of activation of the contact
system. A two- to sixfold increase in the concentrations of tissue
plasminogen activator (t-PA) and von Willebrand factor antigen indicated
endothelial cell activation. This increase started at 120 and 90 minutes,
respectively. The release of t-PA coincided with activation of the
fibrinolytic pathway, as measured by plasmin-alpha 2-antiplasmin complexes.
The fibrinolytic activity of t-PA was subsequently offset by release of
plasminogen activator inhibitor, observed 150 minutes after the endotoxin
injection, and reaching a peak at 240 minutes. No complement activation was
detected. These results show that in humans endotoxin induces an early,
rapidly counteracted fibrinolytic response, and a more long-lasting
activation of thrombin by a mechanism other than contact system activation.
In addition, our data suggest that endotoxin-induced leukopenia and
endothelial cell activation are mediated by TNF.
Volume 76,
Issue 12,
pp. 2520-2526,
12/15/1990
Copyright © 1990 by The American Society of Hematology
 CiteULike  Connotea  Del.icio.us  Digg  Reddit  Technorati What's this?
This article has been cited by other articles:
|
|
|
|
 
V. Stadlbauer, R. P. Mookerjee, G. A. K. Wright, N. A. Davies, G. Jurgens, S. Hallstrom, and R. Jalan
Role of Toll-like receptors 2, 4, and 9 in mediating neutrophil dysfunction in alcoholic hepatitis
Am J Physiol Gastrointest Liver Physiol,
January 1, 2009;
296(1):
G15 - G22.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
T. Gautier, A. Klein, V. Deckert, C. Desrumaux, N. Ogier, A.-L. Sberna, C. Paul, N. Le Guern, A. Athias, T. Montange, et al.
Effect of Plasma Phospholipid Transfer Protein Deficiency on Lethal Endotoxemia in Mice
J. Biol. Chem.,
July 4, 2008;
283(27):
18702 - 18710.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
R. Krogh-Madsen, P. Plomgaard, T. Akerstrom, K. Moller, O. Schmitz, and B. K. Pedersen
Effect of short-term intralipid infusion on the immune response during low-dose endotoxemia in humans
Am J Physiol Endocrinol Metab,
February 1, 2008;
294(2):
E371 - E379.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
C. Erridge, T. Attina, C. M Spickett, and D. J Webb
A high-fat meal induces low-grade endotoxemia: evidence of a novel mechanism of postprandial inflammation
Am. J. Clinical Nutrition,
November 1, 2007;
86(5):
1286 - 1292.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
M. Bahador and A. S. Cross
Review: From therapy to experimental model: a hundred years of endotoxin administration to human subjects
Innate Immunity,
October 1, 2007;
13(5):
251 - 279.
[Abstract]
[PDF]
|
|
|
|
|
|
|
M. K. Huntington, J. F. Williams, and C. D. Mackenzie
Endotoxin contamination in the dental surgery
J. Med. Microbiol.,
September 1, 2007;
56(9):
1230 - 1234.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
K. Ono, C. Nishitani, H. Mitsuzawa, T. Shimizu, H. Sano, H. Suzuki, T. Kodama, N. Fujii, K. Fukase, K. Hirata, et al.
Mannose-Binding Lectin Augments the Uptake of Lipid A, Staphylococcus aureus, and Escherichia coli by Kupffer Cells through Increased Cell Surface Expression of Scavenger Receptor A
J. Immunol.,
October 15, 2006;
177(8):
5517 - 5523.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
R. Renckens, J. J. T. H. Roelofs, S. Florquin, A. F. de Vos, J. M. Pater, H. R. Lijnen, P. Carmeliet, C. van 't Veer, and T. van der Poll
Endogenous Tissue-Type Plasminogen Activator Is Protective during Escherichia coli-Induced Abdominal Sepsis in Mice
J. Immunol.,
July 15, 2006;
177(2):
1189 - 1196.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
M. J. Delano and L. L. Moldawer
The Origins of Cachexia in Acute and Chronic Inflammatory Diseases
Nutr Clin Pract,
February 1, 2006;
21(1):
68 - 81.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
J.-L. Vincent and E. Abraham
The Last 100 Years of Sepsis
Am. J. Respir. Crit. Care Med.,
February 1, 2006;
173(3):
256 - 263.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
S. Zeerleder, C. E. Hack, and W. A. Wuillemin
Disseminated Intravascular Coagulation in Sepsis
Chest,
October 1, 2005;
128(4):
2864 - 2875.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
R. Bisoendial, J. Kastelein, and E. Stroes
Letter to the Editor: In response to van den Berg et al:
Circ. Res.,
September 30, 2005;
97(7):
e71 - e71.
[Full Text]
[PDF]
|
|
|
|
|
|
|
S. Q. van Veen, A. K. van Vliet, M. Wulferink, R. Brands, M. A. Boermeester, and T. M. van Gulik
Bovine Intestinal Alkaline Phosphatase Attenuates the Inflammatory Response in Secondary Peritonitis in Mice
Infect. Immun.,
July 1, 2005;
73(7):
4309 - 4314.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
B. Dixon, J. Santamaria, and D. Campbell
Coagulation Activation and Organ Dysfunction Following Cardiac Surgery
Chest,
July 1, 2005;
128(1):
229 - 236.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
F. B. Mayr, A. Spiel, J. Leitner, C. Marsik, P. Germann, R. Ullrich, O. Wagner, and B. Jilma
Effects of Carbon Monoxide Inhalation during Experimental Endotoxemia in Humans
Am. J. Respir. Crit. Care Med.,
February 15, 2005;
171(4):
354 - 360.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
H. J. Robertshaw and F. M. Brennan
Release of tumour necrosis factor {alpha} (TNF{alpha}) by TNF{alpha} cleaving enzyme (TACE) in response to septic stimuli in vitro
Br. J. Anaesth.,
February 1, 2005;
94(2):
222 - 228.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
R. Guo, Y. Wang, A. W. Minto, R. J. Quigg, and P. N. Cunningham
Acute Renal Failure in Endotoxemia is Dependent on Caspase Activation
J. Am. Soc. Nephrol.,
December 1, 2004;
15(12):
3093 - 3102.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
L. B. Ware, M. D. Eisner, B. T. Thompson, P. E. Parsons, and M. A. Matthay
Significance of Von Willebrand Factor in Septic and Nonseptic Patients with Acute Lung Injury
Am. J. Respir. Crit. Care Med.,
October 1, 2004;
170(7):
766 - 772.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
T. Sprong, A.-S. W. Moller, A. Bjerre, E. Wedege, P. Kierulf, J. W. M. van der Meer, P. Brandtzaeg, M. van Deuren, and T. E. Mollnes
Complement Activation and Complement-Dependent Inflammation by Neisseria meningitidis Are Independent of Lipopolysaccharide
Infect. Immun.,
June 1, 2004;
72(6):
3344 - 3349.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
D. Monakier, M. Mates, M. W. Klutstein, J. A. Balkin, B. Rudensky, D. Meerkin, and D. Tzivoni
Rofecoxib, a COX-2 Inhibitor, Lowers C-Reactive Protein and Interleukin-6 Levels in Patients With Acute Coronary Syndromes
Chest,
May 1, 2004;
125(5):
1610 - 1615.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
R. Renckens, S. Weijer, A. F. de Vos, J. M. Pater, J. C. Meijers, C. E. Hack, M. Levi, and T. van der Poll
Inhibition of Plasmin Activity by Tranexamic Acid Does Not Influence Inflammatory Pathways During Human Endotoxemia
Arterioscler. Thromb. Vasc. Biol.,
March 1, 2004;
24(3):
483 - 488.
[Abstract]
[Full Text]
|
|
|
|
|
|
|
P. Dettenmeier, B. Swindell, M. Stroud, N. Arkins, and A. Howard
Role of Activated Protein C in the Pathophysiology of Severe Sepsis
Am. J. Crit. Care.,
November 1, 2003;
12(6):
518 - 524.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
M. Levi, T. T Keller, E. van Gorp, and H. ten Cate
Infection and inflammation and the coagulation system
Cardiovasc Res,
October 15, 2003;
60(1):
26 - 39.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
T. T Keller, A. T.A Mairuhu, M. D de Kruif, S. K Klein, V. E.A Gerdes, H. ten Cate, D. P.M Brandjes, M. Levi, and E. C.M van Gorp
Infections and endothelial cells
Cardiovasc Res,
October 15, 2003;
60(1):
40 - 48.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
S. Zeerleder, C. Caliezi, G. van Mierlo, A. Eerenberg-Belmer, I. Sulzer, C. E. Hack, and W. A. Wuillemin
Administration of C1 Inhibitor Reduces Neutrophil Activation in Patients with Sepsis
Clin. Vaccine Immunol.,
July 1, 2003;
10(4):
529 - 535.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
S M Pastores
Drotrecogin alfa (activated): a novel therapeutic strategy for severe sepsis
Postgrad. Med. J.,
January 1, 2003;
79(927):
5 - 10.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
G. L. Su
Lipopolysaccharides in liver injury: molecular mechanisms of Kupffer cell activation
Am J Physiol Gastrointest Liver Physiol,
August 1, 2002;
283(2):
G256 - G265.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
I. W. FONG
Infections and their role in atherosclerotic vascular disease
J Am Dent Assoc,
June 1, 2002;
133(suppl_1):
7S - 13S.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
P. N. Cunningham, H. M. Dyanov, P. Park, J. Wang, K. A. Newell, and R. J. Quigg
Acute Renal Failure in Endotoxemia Is Caused by TNF Acting Directly on TNF Receptor-1 in Kidney
J. Immunol.,
June 1, 2002;
168(11):
5817 - 5823.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
Y. Nakagawa, H. Maeda, and T. Murai
Evaluation of the In Vitro Pyrogen Test System Based on Proinflammatory Cytokine Release from Human Monocytes: Comparison with a Human Whole Blood Culture Test System and with the Rabbit Pyrogen Test
Clin. Vaccine Immunol.,
May 1, 2002;
9(3):
588 - 597.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
P. J. Van Ess, M. P. Mattson, and R. A. Blouin
Enhanced Induction of Cytochrome P450 Enzymes and CAR Binding in TNF (p55-/-/p75-/-) Double Receptor Knockout Mice Following Phenobarbital Treatment
J. Pharmacol. Exp. Ther.,
March 1, 2002;
300(3):
824 - 830.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
P. Brandtzaeg, A. Bjerre, R. Ovstebo, B. Brusletto, G. B. Joo, and P. Kierulf
Invited review: Neisseria meningitidis lipopolysaccharides in human pathology
Innate Immunity,
December 1, 2001;
7(6):
401 - 420.
[Abstract]
[PDF]
|
|
|
|
|
|
|
K. E. WELTY-WOLF, M. S. CARRAWAY, D. L. MILLER, T. L. ORTEL, M. EZBAN, A. J. GHIO, S. IDELL, and C. A. PIANTADOSI
Coagulation Blockade Prevents Sepsis-induced Respiratory and Renal Failure in Baboons
Am. J. Respir. Crit. Care Med.,
November 15, 2001;
164(10):
1988 - 1996.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
B. L. Warren, A. Eid, P. Singer, S. S. Pillay, P. Carl, I. Novak, P. Chalupa, A. Atherstone, I. Penzes, A. Kubler, et al.
High-Dose Antithrombin III in Severe Sepsis: A Randomized Controlled Trial
JAMA,
October 17, 2001;
286(15):
1869 - 1878.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
A. Takamiya, M. Takeda, A. Yoshida, and H. Kiyama
Expression of Serine Protease Inhibitor 3 in Ocular Tissues in Endotoxin-Induced Uveitis in Rat
Invest. Ophthalmol. Vis. Sci.,
October 1, 2001;
42(11):
2427 - 2433.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
T. Kadokami, C. F. McTiernan, T. Kubota, C. S. Frye, G. S. Bounoutas, P. D. Robbins, S. C. Watkins, and A. M. Feldman
Effects of soluble TNF receptor treatment on lipopolysaccharide-induced myocardial cytokine expression
Am J Physiol Heart Circ Physiol,
May 1, 2001;
280(5):
H2281 - H2291.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
S. Dunzendorfer, N. Kaneider, A. Rabensteiner, C. Meierhofer, C. Reinisch, J. Romisch, and C. J. Wiedermann
Cell-surface heparan sulfate proteoglycan-mediated regulation of human neutrophil migration by the serpin antithrombin III
Blood,
February 15, 2001;
97(4):
1079 - 1085.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
P. Lohrer, J. Gloddek, A. C. Nagashima, Z. Korali, U. Hopfner, M. P. Pereda, E. Arzt, G. K. Stalla, and U. Renner
Lipopolysaccharide Directly Stimulates the Intrapituitary Interleukin-6 Production by Folliculostellate Cells via Specific Receptors and the p38{{alpha}} Mitogen-Activated Protein Kinase/Nuclear Factor-{{kappa}}B Pathway
Endocrinology,
December 1, 2000;
141(12):
4457 - 4465.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
P. A. Sakkinen, P. Wahl, M. Cushman, M. R. Lewis, and R. P. Tracy
Clustering of Procoagulation, Inflammation, and Fibrinolysis Variables with Metabolic Factors in Insulin Resistance Syndrome
Am. J. Epidemiol.,
November 15, 2000;
152(10):
897 - 907.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
M. Storck, K. Buttenschoen, D. Berger, A. Hannekum, and E. Boelke
Endotoxemia and Mediator Release During Cardiac Surgery
Angiology,
September 1, 2000;
51(9):
743 - 749.
[Abstract]
[PDF]
|
|
|
|
|
|
|
R. F. Franco, E. de Jonge, P. E. P. Dekkers, J. J. Timmerman, C. A. Spek, S. J. H. van Deventer, P. van Deursen, L. van Kerkhoff, B. van Gemen, H. ten Cate, et al.
The in vivo kinetics of tissue factor messenger RNA expression during human endotoxemia: relationship with activation of coagulation
Blood,
July 15, 2000;
96(2):
554 - 559.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
P. M. Ridker, N. Rifai, M. J. Stampfer, and C. H. Hennekens
Plasma Concentration of Interleukin-6 and the Risk of Future Myocardial Infarction Among Apparently Healthy Men
Circulation,
April 18, 2000;
101(15):
1767 - 1772.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
T. Pernerstorfer, U. Hollenstein, J.-B. Hansen, P. Stohlawetz, H.-G. Eichler, S. Handler, W. Speiser, and B. Jilma
| |
