title: Glucocorticoid receptor function is decreased in neutrophils during endotoxic shock.
abstract: OBJECTIVE
  It remains unclear whether glucocorticoid treatment can improve the outcome of sepsis. The aim of the present study was to investigate if glucocorticoid receptor (GR) expression and function is impaired in lipopolysaccharide (LPS) induced shock, and whether the time point for start of glucocorticoid treatment affects the outcome.
  
  
  METHODS
  Male C57BL/6J mice were administered LPS i.p. and GR expression and binding ability in blood and spleen leukocytes were analysed by flow cytometry. GR translocation was analysed using Image Stream technique. The effect of dexamethasone treatment started 2 h before or 2, 12 or 36 h after LPS administration on survival was studied.
  
  
  RESULTS
  Despite increased GR expression in neutrophils after LPS administration, the GR binding capacity was reduced. In addition, GR translocation was decreased in neutrophils and T lymphocytes from endotoxic mice at 12 h compared to control animals. Dexamethasone treatment improved survival only when started early (2 h) after LPS administration.
  
  
  CONCLUSIONS
  The decreased glucocorticoid responsiveness displayed by neutrophils, in combination with their increased numbers, may explain why survival is increased only when dexamethasone treatment is given early during LPS induced shock.
authors.affiliation: Department of Medical Sciences, The Hedenstierna Laboratory, Uppsala University, Sweden; Department of Rheumatology and Inflammation Research, Sahlgrenska Academy, University of Gothenburg, Sweden. Electronic address: maria.bergquist@medsci.uu.se.
authors.forename: Maria
authors.initials: M
authors.lastname: Bergquist
authors.affiliation: Department of Rheumatology and Inflammation Research, Sahlgrenska Academy, University of Gothenburg, Sweden.
authors.forename: Pernilla
authors.initials: P
authors.lastname: Jirholt
authors.affiliation: Department of Rheumatology and Inflammation Research, Sahlgrenska Academy, University of Gothenburg, Sweden.
authors.forename: Merja
authors.initials: M
authors.lastname: Nurkkala
authors.affiliation: Department of Anaesthesia & Intensive Care, Sahlgrenska University Hospital, Gothenburg, Sweden.
authors.forename: Christian
authors.initials: C
authors.lastname: Rylander
authors.affiliation: Department of Medical Sciences, The Hedenstierna Laboratory, Uppsala University, Sweden.
authors.forename: Göran
authors.initials: G
authors.lastname: Hedenstierna
authors.affiliation: Department of Rheumatology and Inflammation Research, Sahlgrenska Academy, University of Gothenburg, Sweden.
authors.forename: Catharina
authors.initials: C
authors.lastname: Lindholm
mesh_terms: D000818:Animals; D016207:Cytokines / Q000097:blood; D003907:Dexamethasone / Q000494:pharmacology; D005786:Gene Expression Regulation; D005938:Glucocorticoids / Q000494:pharmacology*; D008070:Lipopolysaccharides / Q000009:adverse effects; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009504:Neutrophils / Q000187:drug effects / Q000378:metabolism*; D011965:Receptors, Glucocorticoid / Q000235:genetics / Q000378:metabolism*; D012772:Shock, Septic / Q000188:drug therapy* / Q000473:pathology*; D013154:Spleen / Q000166:cytology / Q000187:drug effects / Q000378:metabolism
chemical_list: D016207:Cytokines; D005938:Glucocorticoids; D008070:Lipopolysaccharides; D011965:Receptors, Glucocorticoid; D003907:Dexamethasone
keywords: Dexamethasone; Endotoxin; Glucocorticoid receptor; Lipopolysaccharide; Sepsis