Inhibiting interleukin-1 and tumor necrosis factor-alpha does not reduce induction of plasminogen activator inhibitor type-1 by endotoxin in rats in vivo.
In experimental animals and humans, intravenous (i.v.) injection of endotoxin induces large increases in circulating plasminogen activator inhibitor type-1 (PAI-1), a major inhibitor of blood fibrinolysis. A similar increase is seen after the injection of interleukin-1 (IL-1) or of tumor necrosis factor-alpha (TNF-alpha), suggesting that these cytokines mediate the induction, by endotoxin, of PAI-1. To test this hypothesis we pretreated rats, before i.v. endotoxin, with compounds that inhibit the formation of cytokines (pentoxifylline; dexamethasone), or with compounds that inhibit the action of these cytokines (anti-TNF antiserum for TNF-alpha; IL-1 receptor antagonist for IL-1). None of these pretreatments affected the induction of PAI-1 synthesis by endotoxin. However, pretreatment did reduce the endotoxin-induced increase in plasma tPA antigen concentration. Thus, the data suggest that, in rats in vivo, TNF-alpha and IL-1 are not significantly involved in the induction of PAI-1 by endotoxin.
Emeis
J J
JJ
Gaubius Laboratory TNO-PG, Leiden, The Netherlands.
Hoekzema
R
R
de Vos
A F
AF
D000818:Animals; D003907:Dexamethasone / Q000494:pharmacology; D004347:Drug Interactions; D004731:Endotoxins / Q000494:pharmacology*; D006801:Humans; D007106:Immune Sera / Q000494:pharmacology; D007375:Interleukin-1 / Q000037:antagonists & inhibitors* / Q000494:pharmacology / Q000502:physiology; D008297:Male; D051379:Mice; D010431:Pentoxifylline / Q000494:pharmacology; D017395:Plasminogen Activator Inhibitor 1 / Q000096:biosynthesis*; D051381:Rats; D017208:Rats, Wistar; D017472:Receptors, Interleukin-1 / Q000037:antagonists & inhibitors; D010959:Tissue Plasminogen Activator / Q000097:blood; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors* / Q000494:pharmacology / Q000502:physiology
D004731:Endotoxins; D007106:Immune Sera; D007375:Interleukin-1; D017395:Plasminogen Activator Inhibitor 1; D017472:Receptors, Interleukin-1; D014409:Tumor Necrosis Factor-alpha; D003907:Dexamethasone; D010959:Tissue Plasminogen Activator; D010431:Pentoxifylline