- 作者：Maria Bergquist ; Merja Nurkkala ; Christian Ryl ; er ; Erik Kristiansson ; G枚ran Hedenstierna ; Catharina Lindholm
- 关键词：Sepsis ; Glucocorticoid receptor ; Corticosteroids ; Inflammation ; Staphylococcus aureus
- 刊名：Journal of Infection
- 出版年：December, 2013
- 年：2013
- 卷：67
- 期：6
- 页码：574-583
- 全文大小：2061 K
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 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聽h聽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聽h) improved clinical outcome as studied by weight gain compared to when treatment was started at later time points (48, 72 and 96聽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.