Download PDF
Thromb Haemost 2002; 88(04): 639-643
DOI: 10.1055/s-0037-1613268
Review Article
Schattauer GmbH

The Endotoxin-induced Plasminogen Activator Inhibitor-1 Increase in Rabbits Is Not Tumor Necrosis Factor-α Dependent and Can Occur in the Absence of Interleukin-1β

Ramón Montes
1   Haemostasis and Thrombosis Research Unit, School of Medicine, University of Navarra, Pamplona, Spain
,
Pablo Rodríguez-Whilhelmi
1   Haemostasis and Thrombosis Research Unit, School of Medicine, University of Navarra, Pamplona, Spain
,
Verónica Hurtado
1   Haemostasis and Thrombosis Research Unit, School of Medicine, University of Navarra, Pamplona, Spain
,
Akihiro Matsukawa
2   Department of Pathology, Kumamoto University School of Medicine, Kumamoto, Japan
,
Marta Montes
3   Pathology Service, Hospital Virgendel Camino, Pamplon a, Spain
,
José Hermida
1   Haemostasis and Thrombosis Research Unit, School of Medicine, University of Navarra, Pamplona, Spain
4   Haematology Service, University Clinic, School of Medicine, University of Navarra, Pamplona, Spain
,
Eduardo Rocha
1   Haemostasis and Thrombosis Research Unit, School of Medicine, University of Navarra, Pamplona, Spain
4   Haematology Service, University Clinic, School of Medicine, University of Navarra, Pamplona, Spain
› Author Affiliations
Further Information

Publication History

Received 28 January 2002

Accepted after resubmission 26 June 2002

Publication Date:
09 December 2017 (online)

Also available at
    Permissions and Reprints

Summary

The plasminogen activator inhibitor-1 (PAI-1)-dependent fibrinolytic inhibition occurring in endotoxemia contributes to disseminated intravascular coagulation (DIC). Previous findings suggest that tumor necrosis factor-α (TNF-α) and interleukin-1β (IL-1β) are responsible for the increase in the level of PAI-1. These observations usually arose from mild endotoxemia models. We analyzed the effect of FR167653, an inhibitor of the TNF-α/IL-1β production, on the PAI-1 levels in rabbits given endotoxin at a dose sufficient to induce DIC: the steep plasma PAI-1 increase was not attenuated by FR167653, in spite of achieving efficient inhibition of the TNF-α production. No IL-1β was detected during endotoxemia. These results suggest that PAI-1 increase might be independent of TNF-α and IL-1β. If these findings applied to humans, therapeutic intervention directing these cytokines would not be useful for the treatment of fibrinolysis in patients with severe sepsis.

Keywords

PAI-1 - endotoxin - TNF-α - IL-1β - DIC
 

  • References

  • 1 Levi M, de Jonge E, van der Poll T, ten Cate H. Disseminated intravascular coagulation. Thromb Haemost 1999; 82: 695-705.
    Article in Thieme ConnectPubMedGoogle Scholar
  • 2 ten Cate H. Pathophysiology of disseminated intravascular coagulation in sepsis. Crit Care Med 2000; 28 (Suppl): S9-S11.
    CrossrefPubMedGoogle Scholar
  • 3 Suffredini AF, Harpel PC, Parrillo JE. Promotion and subsequent inhibition of plasminogen activator after administration of intravenous endotoxin to normal subjects. N Engl J Med 1989; 320: 1165-72.
    CrossrefPubMedGoogle Scholar
  • 4 Biemond BJ, Levi M, Ten Cate H, Van der Poll T, Buller HR, Hack CE, Ten Cate JW. Plasminogen activator and plasminogen activator inhibitor I release during experimental endotoxaemia in chimpanzees: effect of interventions in the cytokine and coagulation cascades. Clin Sci 1995; 88: 587-94.
    CrossrefPubMedGoogle Scholar
  • 5 van der Poll T, Levi M, van Deventer SJ, ten Cate H, Haagmans BL, Biemond BJ, Buller HR, Hack CE, ten Cate JW. Differential effects of anti-tumor necrosis factor monoclonal antibodies on systemic inflammatory responses in experimental endotoxemia in chimpanzees. Blood 1994; 83: 446-51.
    PubMedGoogle Scholar
  • 6 van der Poll T, Levi M, Buller HR, van Deventer SJ, de Boer JP, Hack CE, ten Cate JW. Fibrinolytic response to tumor necrosis factor in healthy subjects. J Exp Med 1991; 174: 729-32.
    CrossrefPubMedGoogle Scholar
  • 7 Seki T, Gelehrter TD. Interleukin-1 induction of type-1 plasminogen activator inhibitor (PAI-1) gene expression in the mouse hepatocyte line, AML 12. J Cell Physiol 1996; 168: 648-56.
    CrossrefPubMedGoogle Scholar
  • 8 Jansen PM, Boermeester MA, Fischer E, de Jong IW, van der Poll T, Moldawer LL, Hack CE, Lowry SF. Contribution of interleukin-1 to activation of coagulation and fibrinolysis, neutrophil degranulation, and the release of secretory-type phospholipase A2 in sepsis: studies in nonhuman primates after interleukin-1 alpha administration and during lethal bacteremia. Blood 1995; 86: 1027-34.
    PubMedGoogle Scholar
  • 9 Boermeester MA, van Leeuwen PA, Coyle SM, Wolbink GJ, Hack CE, Lowry SF. Interleukin-1 blockade attenuates mediator release and dysregulation of the hemostatic mechanism during human sepsis. Arch Surg 1995; 130: 739-48.
    CrossrefPubMedGoogle Scholar
  • 10 Hermida J, Montes R, Páramo JA, Rocha E. Endotoxin-induced disseminated intravascular coagulation in rabbits: effect of recombinant hirudin on hemostatic parameters, fibrin deposits, and mortality. J Lab Clin Med 1998; 131: 77-83.
    CrossrefPubMedGoogle Scholar
  • 11 Yamamoto N, Sakai F, Yamazaki H, Nakahara K, Okuhara M. Effect of FR167653, a cytokine suppressive agent, on endotoxin-induced disseminated intravascular coagulation. Eur J Pharmacol 1996; 314: 137-42.
    CrossrefPubMedGoogle Scholar
  • 12 Yamamoto N, Sakai F, Yamazaki H, Sato N, Nakahara K, Okuhara M. FR167653, a dual inhibitor of interleukin-1 and tumor necrosis factoralpha, ameliorates endotoxin-induced shock. Eur J Pharmacol 1997; 327: 169-74.
    CrossrefPubMedGoogle Scholar
  • 13 Takahashi S, Keto Y, Fujita T, Uchiyama T, Yamamoto A. FR167653, a p38 mitogen-activated protein kinase inhibitor, prevents Helicobacter pylori-induced gastritis in Mongolian gerbils. J Pharmacol Exp Ther 2001; 296: 48-56.
    PubMedGoogle Scholar
  • 14 Yoshinari D, Takeyoshi I, Koibuchi Y, Matsumoto K, Kawashima Y, Koyama T, Ohwada S, Morishita Y. Effects of a dual inhibitor of tumor necrosis factor-alpha and interleukin-1 on lipopolysaccharide-induced lung injury in rats: involvement of the p38 mitogen-activated protein kinase pathway. Crit Care Med 2001; 29: 628-34.
    CrossrefPubMedGoogle Scholar
  • 15 Aggarwal BB, Kohr WH. Human tumour necrosis factor. In: Methods in enzymology. Vol. 116. DiSabato G. ed. 1985: 448-56.
    Google Scholar
  • 16 Matsukawa A, Yoshimura T, Miyamoto K, Ohkawara S, Yoshinaga M. Analysis of the inflammatory cytokine network among TNF alpha, IL-1beta, IL-1 receptor antagonist, and IL-8 in LPS-induced rabbit arthritis. Lab Invest 1997; 76: 629-38.
    PubMedGoogle Scholar
  • 17 Montes R, Declerck PJ, Calvo A, Montes M, Hermida J, Muñoz MC, Rocha E. Prevention of renal fibrin deposition in endotoxin-induced DIC through inhibition of PAI-1. Thromb Haemost 2000; 84: 65-70.
    Article in Thieme ConnectPubMedGoogle Scholar
  • 18 Muñoz MC, Montes R, Hermida J, Orbe J, Paramo JA, Rocha E. Effect of the administration of recombinant hirudin and/or tissue-plasminogen activator (t-PA) on endotoxin-induced disseminated intravascular coagulation model in rabbits. Br J Haematol 1999; 105: 117-21.
    CrossrefPubMedGoogle Scholar
  • 19 Gando S, Kameue T, Nanzaki S, Nakanishi Y. Disseminated intravascular coagulation is a frequent complication of systemic inflammatory response syndrome. Thromb Haemost 1996; 75: 224-8.
    Article in Thieme ConnectPubMedGoogle Scholar
  • 20 Gando S, Nakanishi Y, Tedo I. Cytokines and plasminogen activator inhibitor-1 in posttrauma disseminated intravascular coagulation: relationship to multiple organ dysfunction syndrome. Crit Care Med 1995; 23: 1835-42.
    CrossrefPubMedGoogle Scholar
  • 21 Levi M, ten Cate H, Bauer KA, van der Poll T, Edgington TS, Buller HR, van Deventer SJ, Hack CE, ten Cate JW, Rosenberg RD. Inhibition of endotoxin-induced activation of coagulation and fibrinolysis by pentoxifylline or by a monoclonal anti-tissue factor antibody in chimpanzees. J Clin Invest 1994; 93: 114-20.
    CrossrefPubMedGoogle Scholar
  • 22 van der Poll T, Coyle SM, Levi M, Jansen PM, Dentener M, Barbosa K, Buurman WA, Hack CE, ten Cate JW, Agosti JM, Lowry SF. Effect of a recombinant dimeric tumor necrosis factor receptor on inflammatory responses to intravenous endotoxin in normal humans. Blood 1997; 89: 3727-34.
    PubMedGoogle Scholar
  • 23 De La Cadena RA, Majluf-Cruz A, Stadnicki A, Tropea M, Reda D, Agosti JM, Colman RW, Suffredini AF. Recombinant tumor necrosis factor receptor p75 fusion protein (TNFR:Fc) alters endotoxin-induced activation of the kinin, fibrinolytic, and coagulation systems in normal humans. Thromb Haemost 1998; 80: 114-8.
    Article in Thieme ConnectPubMedGoogle Scholar
  • 24 Sprengers ED, Kluft C. Plasminogen activator inhibitors. Blood 1987; 69: 381-7.
    PubMedGoogle Scholar
  • 25 Emeis JJ, Hoekzema R, de Vos AF. Inhibiting interleukin-1 and tumor necrosis factor-alpha does not reduce induction of plasminogen activator inhibitor type-1 by endotoxin in rats in vivo. Blood 1995; 85: 115-20.
    PubMedGoogle Scholar
  • 26 Kornelisse RF, Hazelzet JA, Savelkoul HF, Hop WC, Suur MH, Borsboom AN, Risseeuw-Appel IM, van der Voort E, de Groot R. The relationship between plasminogen activator inhibitor-1 and proinflammatory and counterinflammatory mediators in children with meningococcal septic shock. J Infect Dis 1996; 173: 1148-56.
    CrossrefPubMedGoogle Scholar