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Ramn Montes, Pablo Rodrguez-Whilhelmi, Vernica Hurtado, Akihiro Matsukawa, Marta Montes, Jos Hermida, Eduardo Rocha
The Endotoxin-induced Plasminogen Activator Inhibitor-1 Increase in Rabbits Is Not Tumor Necrosis Factor- Dependent and Can Occur in the Absence of Interleukin-1
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- (TNF-) and interleukin-1 (IL-1) 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-/IL-1 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- production. No IL-1 was detected during endotoxemia. These results suggest that PAI-1 increase might be independent of TNF- and IL-1. 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.
Thrombosis and Haemostasis, Schattauer
Print ISSN: 0340-6245
Volume: 88, 01/2002
Pages: 639 - 643