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