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Colon Ascendens Stent Peritonitis CASP - a Standardized Model for Polymicrobial Abdominal Sepsis
Published on: December 18, 2010
Osteopontin is associated with inflammation and mortality in a mouse model of polymicrobial sepsis
S Fortis1, R G Khadaroo, J J Haitsma
1Keenan Research Center for Biomedical Science, St. Michael's Hospital, Toronto, ON, Canada; Department of Anaesthesia, University of Toronto, Toronto, ON, Canada; Interdepartmental Division of Critical Care Medicine, University of Toronto, Toronto, ON, Canada; Department of Physiology, University of Toronto, Toronto, ON, Canada.
Background:
Osteopontin (OPN) is a multifunctional glycoprotein with pro-inflammatory properties. In severe sepsis, levels of plasma OPN are significantly higher in non-survivors than in survivors. We hypothesized that OPN results in greater inflammation and worse outcome through modulation of endogenous glucocorticoid production in sepsis.
Methods And Results:
Sepsis was induced by cecal ligation and puncture (CLP) in wild type (WT) and OPN gene knockout (OPN(-/-) ) mice. In response to sepsis, the OPN(-/-) mice had lower levels of plasma cytokines and chemokines than the WT mice. The levels of corticosterone in plasma were similar between WT and OPN(-/-) sham animals but they increased 24 h after CLP induction in the WT mice, but not in the OPN(-/-) mice. The mortality rate was lower in the OPN(-/-) mice than in the WT mice.
Conclusion:
OPN is associated with greater inflammatory response and increased mortality, despite the higher corticosterone levels in plasma. Corticosterone production is not impaired in the absence of OPN.

