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 language | English |
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Pages (from-to) | 639-643 |
Number of pages | 5 |
Journal | Thrombosis and Haemostasis |
Volume | 88 |
Issue number | 4 |
DOIs | |
Publication status | Published - Oct 1 2002 |
Externally published | Yes |
Keywords
- DIC
- Endotoxin
- IL-1β
- PAI-1
- TNF-α
ASJC Scopus subject areas
- Hematology