Expression of the glucocorticoid receptor is decreased in experimental Staphylococcus aureus sepsis.
Artikel i vetenskaplig tidskrift, 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.

Författare

Maria Bergquist

Göteborgs universitet

Merja Nurkkala

Göteborgs universitet

Christian Rylander

Sahlgrenska universitetssjukhuset

Erik Kristiansson

Chalmers, Matematiska vetenskaper, matematisk statistik

Göteborgs universitet

Göran Hedenstierna

Uppsala universitet

Catharina Lindholm

Göteborgs universitet

The Journal of infection

1532-2742 (eISSN)

Vol. 67 574-583

Ämneskategorier

Anestesi och intensivvård

Infektionsmedicin

DOI

10.1016/j.jinf.2013.07.028

PubMed

23933016