Oct, 2002
The endotoxin-induced plasminogen activator inhibitor-1 increase in rabbits is not tumor necrosis factor-alpha dependent and can occur in the absence of interleukin-1 beta
THROMBOSIS AND HAEMOSTASIS
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- Volume
- 88
- Number
- 4
- First page
- 639
- Last page
- 643
- Language
- English
- Publishing type
- Research paper (scientific journal)
- Publisher
- SCHATTAUER GMBH-VERLAG MEDIZIN NATURWISSENSCHAFTEN
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-alpha (TNF-alpha) and interleukin-1beta (IL-1beta) 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-alpha/IL-1beta 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-alpha production. No IL-1beta was detected during endotoxemia. These results suggest that PAI-1 increase might be independent of TNF-alpha and IL-1beta. 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.
- Link information
- ID information
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- ISSN : 0340-6245
- Pubmed ID : 12362236
- Web of Science ID : WOS:000178660900016