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 |
|---|---|
| Pages (from-to) | 639-643 |
| Number of pages | 5 |
| Journal | Thrombosis and Haemostasis |
| Volume | 88 |
| Issue number | 4 |
| Publication status | Published - Oct 1 2002 |
| Externally published | Yes |
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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 journal › Article
}
TY - JOUR
T1 - 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
AU - Montes, Ramón
AU - Rodríguez-Whilhelmi, Pablo
AU - Hurtado, Verónica
AU - Matsukawa, Akihiro
AU - Montes, Marta
AU - Hermida, José
AU - Rocha, Eduardo
PY - 2002/10/1
Y1 - 2002/10/1
N2 - 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.
AB - 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.
KW - DIC
KW - Endotoxin
KW - IL-1β
KW - PAI-1
KW - TNF-α
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M3 - Article
VL - 88
SP - 639
EP - 643
JO - Thrombosis and Haemostasis
JF - Thrombosis and Haemostasis
SN - 0340-6245
IS - 4
ER -