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Glucocorticoid receptor expression and binding capacity in patients with burn injury
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Physiology.
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Plastic Surgery.ORCID iD: 0000-0002-9735-1434
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2016 (English)In: Acta Anaesthesiologica Scandinavica, ISSN 0001-5172, E-ISSN 1399-6576, Vol. 60, no 2, 213-221 p.Article in journal (Refereed) Published
Abstract [en]

Background

Burn injuries are associated with strong inflammation and risk of secondary sepsis which both may affect the function of the glucocorticoid receptor (GR). The aim of this study was to determine GR expression and binding capacity in leucocytes from patients admitted to a tertiary burn center.

Methods

Blood was sampled from 13 patients on admission and days 7, 14 and 21, and once from 16 healthy subjects. Patients were grouped according to the extent of burn and to any sepsis on day 7. Expression and binding capacity of GR were determined as arbitrary units using flow cytometry.

Results

GR expression and binding capacity were increased compared to healthy subjects in most circulating leucocyte subsets on admission irrespective of burn size. Patients with sepsis on day 7 displayed increased GR expression in T lymphocytes (51.8%, < 0.01) compared to admission. There was a negative correlation between GR binding capacity in neutrophils and burn size after 14 days (< 0.05).

Conclusions

GR expression and binding capacity are increased in most types of circulating leucocytes of severely burned patients on their admission to specialized burn care. If sepsis is present after 1 week, it is associated with higher GR expression in T lymphocytes and NK cells.

Place, publisher, year, edition, pages
2016. Vol. 60, no 2, 213-221 p.
National Category
Cell and Molecular Biology
Identifiers
URN: urn:nbn:se:uu:diva-229116DOI: 10.1111/aas.12604ISI: 000368139700009OAI: oai:DiVA.org:uu-229116DiVA: diva2:735719
Funder
Swedish Research Council, 5315
Available from: 2014-07-31 Created: 2014-07-31 Last updated: 2017-12-05
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)
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Supervisors
Available from: 2014-09-04 Created: 2014-07-31 Last updated: 2014-09-08

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Bergquist, MariaHuss, FredrikMartijn, CecileHedenstierna, GöranFredén, Filip

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