title: Osteopontin is associated with inflammation and mortality in a mouse model of polymicrobial sepsis.
abstract: 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.
  
  
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Keenan 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.
authors.forename: S
authors.initials: S
authors.lastname: Fortis
authors.forename: R G
authors.initials: RG
authors.lastname: Khadaroo
authors.forename: J J
authors.initials: JJ
authors.lastname: Haitsma
authors.forename: H
authors.initials: H
authors.lastname: Zhang
mesh_terms: D000818:Animals; D003345:Corticosterone / Q000097:blood; D016207:Cytokines / Q000097:blood; D004195:Disease Models, Animal; D007249:Inflammation / Q000097:blood* / Q000401:mortality*; D015850:Interleukin-6 / Q000097:blood; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D053495:Osteopontin / Q000097:blood*; D018805:Sepsis / Q000097:blood* / Q000401:mortality*; D014409:Tumor Necrosis Factor-alpha / Q000097:blood
chemical_list: D016207:Cytokines; D015850:Interleukin-6; D014409:Tumor Necrosis Factor-alpha; D053495:Osteopontin; D003345:Corticosterone