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Expression of the glucocorticoid receptor is decreased in experimental Staphylococcus aureus sepsis.

Journal article
Authors Maria Bergquist
Merja Nurkkala
Christian Rylander
Erik Kristiansson
Göran Hedenstierna
Catharina Lindholm
Published in The Journal of infection
Volume 67
Issue 6
Pages 574–583
ISSN 1532-2742
Publication year 2013
Published at Department of Mathematical Sciences, Mathematical Statistics
Institute of Medicine, Department of Rheumatology and Inflammation Research
Pages 574–583
Language en
Links dx.doi.org/10.1016/j.jinf.2013.07.0...
Subject categories Anesthesiology and Intensive Care, Infectious Medicine

Abstract

Introduction Glucocorticoid treatment in septic shock remains controversial after recent trials. We hypothesized that failure to respond to steroid therapy may be caused by decreased expression and/or function of glucocorticoid receptors (GR) and studied this in a mouse model of Staphylococcus aureus sepsis. The impact of timing of dexamethasone treatment was also investigated. Methods Male C57BL/6J mice were intravenously inoculated with S. aureus and GR expression and binding ability in blood, spleen and lymph nodes were analysed by means of flow cytometry. GR translocation was analysed using Image Stream. Septic mice were administered dexamethasone at 22, 26, 48, 72 and 96 h after inoculation and body weight, as a sign of dehydration, was observed. Results GR expression was decreased in septic animals, but not the ligand binding capacity. GR translocation was decreased in septic mice compared to control animals. Early dexamethasone treatment (22 and 26 h) improved clinical outcome as studied by weight gain compared to when treatment was started at later time points (48, 72 and 96 h). Conclusion Our data provide evidence that GR expression is progressively decreased in experimental sepsis and that dexamethasone has a decreased ability to translocate into the cell nucleus. This may explain why steroid treatment is only beneficial when administered early in sepsis and septic shock.

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