Expression of the glucocorticoid receptor is decreased in experimental Staphylococcus aureus sepsis.
Journal article, 2013

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.

Author

Maria Bergquist

University of Gothenburg

Merja Nurkkala

University of Gothenburg

Christian Rylander

Sahlgrenska University Hospital

Erik Kristiansson

Chalmers, Mathematical Sciences, Mathematical Statistics

University of Gothenburg

Göran Hedenstierna

Uppsala University

Catharina Lindholm

University of Gothenburg

Journal of Infection

0163-4453 (ISSN)

Vol. 67 6 574-583

Subject Categories

Anesthesiology and Intensive Care

Infectious Medicine

DOI

10.1016/j.jinf.2013.07.028

PubMed

23933016

More information

Latest update

10/5/2023