Inhibiting interleukin-1 and tumor necrosis factor-α does not reduce induction of plasminogen activator inhibitor type-1 by endotoxin in rats in vivo

article


Emeis, J.E.

Hoekzema, R.

Vos, A.F. de
In experimental animals and humans, intravenous (IV) 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-α (TNF-α), suggesting that these cytokines mediate the induction, by endotoxin, of PAI-1. To test this hypothesis we pretreated rats, before IV 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-α; 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-α and IL-1 are not significantly involved in the induction of PAI-1 by endotoxin. Chemicals/CAS: corticosterone, 50-22-6; dexamethasone, 50-02-2; pentoxifylline, 6493-05-6; plasminogen activator inhibitor 1, 140208-23-7; tissue plasminogen activator, 105913-11-9; Dexamethasone, 50-02-2; Endotoxins; Immune Sera; Interleukin-1; Pentoxifylline, 6493-05-6; Plasminogen Activator Inhibitor 1; Receptors, Interleukin-1; Tissue Plasminogen Activator, EC 3.4.21.68; Tumor Necrosis Factor
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corticosteronedexamethasoneescherichia coli endotoxinescherichia coli lipopolysaccharideinterleukin 1interleukin 1 receptor blocking agentpentoxifyllineplasminogen activator inhibitor 1tissue plasminogen activatortumor necrosis factor alphaanimal experimentanimal modelarticledrug effectdrug screeningendotoxemiaintravenous drug administrationmalenonhumanpriority journalrattoxicity testingtoxin analysisAnimalDexamethasoneDrug InteractionsEndotoxinsHumanImmune SeraInterleukin-1MaleMicePentoxifyllinePlasminogen Activator Inhibitor 1RatsRats, WistarReceptors, Interleukin-1Tissue Plasminogen ActivatorTumor Necrosis Factor
TNO Identifier
232831
Repository link
https://resolver.tno.nl/uuid:9d75dc7c-d245-421e-b7fd-09d7c1a8af30
ISSN
00064971
Source
Blood, 85(1), pp. 115-120.
Pages
115-120
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