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

doi:10.1055/s-0037-1613268

Thrombosis and Haemostasis, Inhaltsverzeichnis

Thromb Haemost 2002; 88(04): 639-643
DOI: 10.1055/s-0037-1613268

Review Article

Schattauer GmbH

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

¹Haemostasis and Thrombosis Research Unit, School of Medicine, University of Navarra, Pamplona, Spain

,

Pablo Rodríguez-Whilhelmi

¹Haemostasis and Thrombosis Research Unit, School of Medicine, University of Navarra, Pamplona, Spain

,

Verónica Hurtado

¹Haemostasis and Thrombosis Research Unit, School of Medicine, University of Navarra, Pamplona, Spain

,

Akihiro Matsukawa

²Department of Pathology, Kumamoto University School of Medicine, Kumamoto, Japan

,

Marta Montes

³Pathology Service, Hospital Virgendel Camino, Pamplon a, Spain

,

José Hermida

¹Haemostasis and Thrombosis Research Unit, School of Medicine, University of Navarra, Pamplona, Spain

⁴Haematology Service, University Clinic, School of Medicine, University of Navarra, Pamplona, Spain

,

Eduardo Rocha

¹Haemostasis and Thrombosis Research Unit, School of Medicine, University of Navarra, Pamplona, Spain

⁴Haematology Service, University Clinic, School of Medicine, University of Navarra, Pamplona, Spain

› Institutsangaben

Abstract

Summary

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.

Keywords

PAI-1 - endotoxin - TNF-α - IL-1β - DIC

Volltext

Referenzen

References
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