uu.seUppsala University Publications
Change search
CiteExportLink to record
Permanent link

Direct link
Cite
Citation style
  • apa
  • ieee
  • modern-language-association
  • vancouver
  • Other style
More styles
Language
  • de-DE
  • en-GB
  • en-US
  • fi-FI
  • nn-NO
  • nn-NB
  • sv-SE
  • Other locale
More languages
Output format
  • html
  • text
  • asciidoc
  • rtf
Glucocorticoid receptor function is decreased in neutrophils during endotoxic shock
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Physiology.
Show others and affiliations
2014 (English)In: Journal of Infection, ISSN 0163-4453, E-ISSN 1532-2742, Vol. 69, no 2, 113-122 p.Article in journal (Refereed) Published
Abstract [en]

OBJECTIVES: 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.

METHODS: 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.

RESULTS: 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.

CONCLUSION: 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.

Place, publisher, year, edition, pages
2014. Vol. 69, no 2, 113-122 p.
National Category
Infectious Medicine
Research subject
Clinical Physiology
Identifiers
URN: urn:nbn:se:uu:diva-223346DOI: 10.1016/j.jinf.2014.03.011ISI: 000339751500002PubMedID: 24657243OAI: oai:DiVA.org:uu-223346DiVA: diva2:713020
Available from: 2014-04-17 Created: 2014-04-17 Last updated: 2017-12-05Bibliographically approved
In thesis
1. Glucocorticoid receptors in severe inflammation: Experimental and clinical studies
Open this publication in new window or tab >>Glucocorticoid receptors in severe inflammation: Experimental and clinical studies
2014 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

Septic shock is one of the most common causes of mortality in intensive care, in spite of antibiotic treatment. Glucocorticoid treatment can be used to blunt an overwhelming immune response in severe inflammation. The varying effects of glucocorticoid treatment in sepsis are poorly understood, with consequences for the clinical guidelines for treatment. Glucocorticoids are potent anti-inflammatory mediators which exert their effects through the glucocorticoid receptor (GR). Deeper understanding about the mechanisms of GR signalling may help to guide and improve glucocorticoid treatment. The aim of this thesis was to analyse GR expression and binding capacity in experimental and human septic shock and severe inflammation with cellular specificity using flow cytometry. In the late phase of a murine sepsis model, we observed decreased GR expression in leukocytes. In a murine model of early endotoxic shock, we observed decreased GR binding capacity in spite of an increased expression, in neutrophils. Glucocorticoid treatment was beneficial only when administered early in both models. Compared to healthy subjects, GR expression was increased in leukocytes from patients during the initial sepsis phase, while GR binding capacity was only increased in lymphocytes and monocytes. In contrast, neutrophils and other leukocyte subsets displayed decreased GR binding capacity. Neutrophil numbers were increased in all patients with sepsis compared to healthy subjects. We also studied patients with burn injury after admission before any infectious event had likely occurred, and on day 7 post admission, when several of the patients had been diagnosed with sepsis. GR expression and binding capacity was increased in leukocytes on admission as compared to healthy subjects, and patients diagnosed with sepsis on day 7 had a further increased GR expression in T lymphocytes. GR binding capacity was decreased in proportion to the extent of the burn injury on day 14 post admission. In conclusion, sepsis and severe inflammation have significant impact on the expression and function of GR, likely to influence the efficiency of glucocorticoid treatment. In addition, glucocorticoid treatment is beneficial only when given early in these models of experimental sepsis.

Place, publisher, year, edition, pages
Uppsala: Acta Universitatis Upsaliensis, 2014. 86 p.
Series
Digital Comprehensive Summaries of Uppsala Dissertations from the Faculty of Medicine, ISSN 1651-6206 ; 1016
Keyword
glucocorticoid receptor, sepsis, inflammation, flow cytometry
National Category
Cell and Molecular Biology
Research subject
Clinical Immunology
Identifiers
urn:nbn:se:uu:diva-229119 (URN)978-91-554-8994-6 (ISBN)
Public defence
2014-09-26, Robergsalen, Ing 40, Uppsala University, Uppsala, 13:00 (English)
Opponent
Supervisors
Available from: 2014-09-04 Created: 2014-07-31 Last updated: 2014-09-08

Open Access in DiVA

No full text

Other links

Publisher's full textPubMed

Authority records BETA

Bergquist, MariaHedenstierna, Göran

Search in DiVA

By author/editor
Bergquist, MariaHedenstierna, Göran
By organisation
Clinical Physiology
In the same journal
Journal of Infection
Infectious Medicine

Search outside of DiVA

GoogleGoogle Scholar

doi
pubmed
urn-nbn

Altmetric score

doi
pubmed
urn-nbn
Total: 418 hits
CiteExportLink to record
Permanent link

Direct link
Cite
Citation style
  • apa
  • ieee
  • modern-language-association
  • vancouver
  • Other style
More styles
Language
  • de-DE
  • en-GB
  • en-US
  • fi-FI
  • nn-NO
  • nn-NB
  • sv-SE
  • Other locale
More languages
Output format
  • html
  • text
  • asciidoc
  • rtf