The effect of activated protein C on plasma cytokine levels in a porcine model of acute endotoxemia.
OBJECTIVE
To assess the anti-inflammatory effects of recombinant human activated protein C (rhAPC) in a porcine model of acute endotoxemia.


METHODS
Animal randomized controlled study at the Laboratory of Clinical Institute, Aarhus University Hospital.


METHODS
Eighteen female landrace pigs (30 kg).


METHODS
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.
Nielsen
Jeppe Sylvest
JS
Aarhus University Hospital, Department of Anesthesiology and Intensive Care Medicine, Nørrebrogade 44, 8000 Aarhus C, Denmark. Sylvest@Ki.au.dk
Larsson
Anders
A
Rix
Thomas
T
Nyboe
Rasmus
R
Gjedsted
Jakob
J
Krog
Jan
J
Ledet
Thomas
T
Tønnesen
Else
E
D000818:Animals; D016207:Cytokines / Q000032:analysis* / Q000276:immunology; D003718:Denmark; D019446:Endotoxemia / Q000097:blood / Q000276:immunology; D011486:Protein C / Q000008:administration & dosage / Q000378:metabolism / Q000493:pharmacokinetics*; D011897:Random Allocation; D011994:Recombinant Proteins; D013552:Swine; D018746:Systemic Inflammatory Response Syndrome
D016207:Cytokines; D011486:Protein C; D011994:Recombinant Proteins; C421124:drotrecogin alfa activated