Abstract
Background: Protein C (PC) is able to reduce the liberation of pro-inflammatory cytokines in sepsis. While this effect was mainly assessed in in-vitro in monocytes and cultured endothelial cells, there is little data on the regulation of interleukin 10 (IL10) by PC in in-vivo sepsis. Furthermore, the action of PC in neonatal septic shock is unclear.
Methods: Endotoxin shock was induced in 10 neonatal piglets under general anesthesia by intravenous application of 500 μg/kg E. coli lipopolysaccharids. 5 piglets received human Protein C concentrate (Ceprotin®, Baxter) with an initial bolus of 50 μg/kg, followed by continuous infusion of 200 μg/kg/d. 5 piglets served as control group. TNF á, Interferon 1ã (IFN ã) and IL10 were measured using porcine immunoassays (TNF á and IL10: R&D Systems, Minneapolis, USA; IFN ã: Biosource, Camarillo, USA) of samples taken at 0,60,120 and180 min after LPS-exposure.
Results: TNF á rapidly increased > 10 fold in all animals after the LPS exposure. The maximum TNF á concentration was reached at 60 min and decreased at 120 and 180 min, although the TNF á levels at 180 min were at least 3 fold above baseline. There was no difference in the course of TNF á whether the animals received PC or not. IFN ã levels remained unchanged in this early phase of septic shock in the animals treated with PC and the controls IL10 levels increased in the control animals but did not reach a 2 fold increase over baseline with a maximum between 60 and 120 min followed by a decrease in IL10 levels. In contrast, the IL 10 levels in the PC treated animals exceeded a 2 fold increase and stayed elevated throughout the study period.
Conclusion: In this animal model PC induced a fast and sustained induction of the anti-inflammatory cytokine IL10 in the early phase of neonatal septic shock. The unchanged levels of IFN ã in all animals might be attributable to the short study time. Surprisingly, the rapid and marked increase of TNF á followed by a subsequent decrease was observed to be unrelated to PC treatment in this animal model of LPS induced neonatal septic shock.
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Veldman, A., Nold, M., Petry, C. et al. 262 Interleukin 10 is UP-Regulated by Human Protein C-Concentrate in The Early Phase of A Neonatal Piglet Model of Septic Shock. Pediatr Res 56, 508 (2004). https://doi.org/10.1203/00006450-200409000-00285
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DOI: https://doi.org/10.1203/00006450-200409000-00285