Objective: To assess the anti-inflammatory effects of recombinant human activated protein C (rhAPC) in a porcine model of acute endotoxemia.
Design and setting: Animal randomized controlled study at the Laboratory of Clinical Institute, Aarhus University Hospital.
Subjects: Eighteen female landrace pigs (30 kg).
Interventions: By pairwise randomization, pigs were given either LPS or LPS and rhAPC. Both groups received a stepwise increasing LPS infusion for 30[Symbol: see text]min; whereafter the infusion continued at a lower rate (300 min LPS in both groups). The LPS+rhAPC group received rhAPC (100 microg/kg per hour) 15 min before the LPS infusion began and throughout the trial period.
Results: While rhAPC showed no modifying effects on peak plasma levels of pro- or anti-inflammatory cytokines (TNF-alpha, IL-6, IL-8, IL-10), TNF-alpha and IL-10 peaked significantly later in the rhAPC-treated animals. The profibrinolytic effects of rhAPC were confirmed by decreased plasminogen activator inhibitor 1 levels, while no differences were found in other coagulation markers, hemodynamic, metabolic, or leukocyte data between the two groups.
Conclusions: We found no significant effect of rhAPC on plasma levels of either pro- or anti-inflammatory cytokines in this porcine model of acute endotoxemia. However, TNF-alpha and IL-10 peaked significantly later in the rhAPC-treated animals.