Department of Medical Sciences, The Hedenstierna Laboratory, Uppsala University, Sweden; Department of Rheumatology and Inflammation Research, Sahlgrenska Academy, University of Gothenburg, Sweden.
Department of Rheumatology and Inflammation Research, Sahlgrenska Academy, University of Gothenburg, Sweden.
J Infect. 2014 Aug;69(2):113-22. doi: 10.1016/j.jinf.2014.03.011. Epub 2014 Mar 19.
It remains unclear whether glucocorticoid treatment can improve the outcome of sepsis. The aim of the present study was to investigate if glucocorticoid receptor (GR) expression and function is impaired in lipopolysaccharide (LPS) induced shock, and whether the time point for start of glucocorticoid treatment affects the outcome.
Male C57BL/6J mice were administered LPS i.p. and GR expression and binding ability in blood and spleen leukocytes were analysed by flow cytometry. GR translocation was analysed using Image Stream technique. The effect of dexamethasone treatment started 2 h before or 2, 12 or 36 h after LPS administration on survival was studied.
Despite increased GR expression in neutrophils after LPS administration, the GR binding capacity was reduced. In addition, GR translocation was decreased in neutrophils and T lymphocytes from endotoxic mice at 12 h compared to control animals. Dexamethasone treatment improved survival only when started early (2 h) after LPS administration.
The decreased glucocorticoid responsiveness displayed by neutrophils, in combination with their increased numbers, may explain why survival is increased only when dexamethasone treatment is given early during LPS induced shock.
糖皮质激素治疗能否改善脓毒症的预后仍不清楚。本研究旨在探讨脂多糖（LPS）诱导性休克是否会损害糖皮质激素受体（GR）的表达和功能，以及糖皮质激素治疗开始的时间点是否会影响预后。
雄性 C57BL/6J 小鼠腹腔内给予 LPS，通过流式细胞术分析血液和脾白细胞中的 GR 表达和结合能力。使用图像流技术分析 GR 易位。研究了在 LPS 给药前 2 小时或给药后 2、12 或 36 小时开始给予地塞米松治疗对存活的影响。
尽管 LPS 给药后中性粒细胞中 GR 表达增加，但 GR 结合能力降低。此外，与对照动物相比，内毒素血症小鼠的中性粒细胞和 T 淋巴细胞中的 GR 易位在 12 小时时减少。只有在 LPS 给药后 2 小时早期开始地塞米松治疗才能改善存活。
中性粒细胞糖皮质激素反应性降低，同时数量增加，这可能解释了为什么只有在 LPS 诱导性休克期间早期给予地塞米松治疗才能提高存活率。
