Tissue factor pathway inhibitor does not influence inflammatory pathways during human endotoxemia

Activation of coagulation induces a proinflammatory response in in vitro an d animal experiments. Inhibition of the tissue factor-dependent pathway of coagulation inhibits cytokine release and prevents death in gram-negative s epsis models in primates. This study investigated the influence of blocking the coagulation system by tissue factor pathway inhibitor (TFPI) on endoto xin-induced inflammatory responses in healthy humans. Eight men were studie d in a double-blind, randomized, placebo-controlled cross-over study. They received a bolus intravenous injection of 4 ng/kg of endotoxin, followed by a 6-h continuous infusion of either TFPI (0.2 mg/kg/h after a bolus of 0.0 5 mg/kg) or placebo. Endotoxin induced-activation of coagulation was preven ted completely by TFPI. In contrast, TFPI did not influence leukocyte activ ation, chemokine release, endothelial cell activation, or the acute phase r esponse. Thus, complete prevention of coagulation activation by TFPI does n ot influence activation of inflammatory pathways during human endotoxemia.