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

Research output: Contribution to journalArticle

12 Citations (Scopus)

Abstract

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
Volume88
Issue number4
Publication statusPublished - Oct 1 2002
Externally publishedYes

Fingerprint

Plasminogen Activator Inhibitor 1
Interleukin-1
Endotoxins
Tumor Necrosis Factor-alpha
Endotoxemia
Rabbits
Disseminated Intravascular Coagulation
Fibrinolysis
Sepsis
Cytokines
Therapeutics
FR 167653

Keywords

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

ASJC Scopus subject areas

  • Hematology

Cite this

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. / Montes, Ramón; Rodríguez-Whilhelmi, Pablo; Hurtado, Verónica; Matsukawa, Akihiro; Montes, Marta; Hermida, José; Rocha, Eduardo.

In: Thrombosis and Haemostasis, Vol. 88, No. 4, 01.10.2002, p. 639-643.

Research output: Contribution to journalArticle

Montes, Ramón ; Rodríguez-Whilhelmi, Pablo ; Hurtado, Verónica ; Matsukawa, Akihiro ; Montes, Marta ; Hermida, José ; Rocha, Eduardo. / 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. In: Thrombosis and Haemostasis. 2002 ; Vol. 88, No. 4. pp. 639-643.
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