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, Pablo Rodríguez-Whilhelmi, Verónica Hurtado, Akihiro Matsukawa, Marta Montes, José Hermida, Eduardo Rocha

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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.

Original languageEnglish
Pages (from-to)639-643
Number of pages5
JournalThrombosis and Haemostasis
Issue number4
Publication statusPublished - Oct 1 2002



  • DIC
  • Endotoxin
  • IL-1β
  • PAI-1
  • TNF-α

ASJC Scopus subject areas

  • Hematology

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