Expression of the glucocorticoid receptor is decreased in experimental Staphylococcus aureus sepsis Maria Bergquist a,b, *, Merja Nurkkala b , Christian Rylander c , Erik Kristiansson d ,Go¨ranHedenstierna a , Catharina Lindholm b a Department of Medical Sciences, The Hedenstierna Laboratory, Uppsala University, Sweden b Department of Rheumatology and Inflammation Research, Sahlgrenska Academy, University of Gothenburg, Sweden c Department of Anesthesia & Intensive Care, Sahlgrenska University Hospital, Gothenburg, Sweden d Department of Mathematical Statistics, Chalmers University of Technology, Gothenburg, Sweden Accepted 31 July 2013 Available online 6 August 2013 KEYWORDS Sepsis; Glucocorticoid receptor; Corticosteroids; Inflammation; Staphylococcus aureus Summary 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 treat- ment 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 experi- mental 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. ª 2013 The British Infection Association. Published by Elsevier Ltd. All rights reserved. * Corresponding author. Uppsala University, The Hedenstierna Laboratory, Ing 40, 3tr, S-75185 Uppsala, Sweden. Tel.: þ46 (0) 18 6115165; fax: þ46 (0) 18 611 41 53. E-mail address: maria.bergquist@medsci.uu.se (M. Bergquist). 0163-4453/$36 ª 2013 The British Infection Association. Published by Elsevier Ltd. All rights reserved. http://dx.doi.org/10.1016/j.jinf.2013.07.028 www.elsevierhealth.com/journals/jinf Journal of Infection (2013) 67, 574e583