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Glucocorticoid receptor function is decreased in neutrophils during endotoxic shock

Authors
  • Bergquist, Maria
  • Jirholt, Pernilla
  • Nurkkala, Merja
  • Rylander, Christian
  • Hedenstierna, Göran
  • Lindholm, Catharina1, 2, 3, 4, 5, 6, 7, 8
  • 1 Department of Medical Sciences
  • 2 The Hedenstierna Laboratory
  • 3 Uppsala University
  • 4 Department of Rheumatology and Inflammation Research
  • 5 Sahlgrenska Academy
  • 6 University of Gothenburg
  • 7 Department of Anaesthesia & Intensive Care
  • 8 Sahlgrenska University Hospital
Type
Published Article
Journal
Journal of Infection
Publisher
Elsevier
Publication Date
Jan 01, 2014
Accepted Date
Mar 11, 2014
Identifiers
DOI: 10.1016/j.jinf.2014.03.011
Source
Elsevier
Keywords
License
Unknown

Abstract

ObjectivesIt 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. MethodsMale 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. ResultsDespite 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. ConclusionThe 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.

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