Glucocorticoid receptors in severe inflammation: Experimental and clinical studies

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MARC

Bergquist, MariaUppsala universitet,Klinisk fysiologi (author)

Glucocorticoid receptors in severe inflammation : Experimental and clinical studies

BookEnglish2014

Publisher, publication year, extent ...

Uppsala :Acta Universitatis Upsaliensis,2014
86 s.
electronicrdacarrier

Numbers

LIBRIS-ID:oai:DiVA.org:uu-229119
ISBN:9789155489946
https://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-229119URI

Supplementary language notes

Language:English
Summary in:English

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SwePubSwePub

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Subject category:vet swepub-contenttype
Subject category:dok swepub-publicationtype

Series

Digital Comprehensive Summaries of Uppsala Dissertations from the Faculty of Medicine,1651-6206 ;1016

Notes

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.

Subject headings and genre

MEDICIN OCH HÄLSOVETENSKAP Medicinska och farmaceutiska grundvetenskaper Cell- och molekylärbiologi hsv//swe
MEDICAL AND HEALTH SCIENCES Basic Medicine Cell and Molecular Biology hsv//eng
glucocorticoid receptor
sepsis
inflammation
flow cytometry
Klinisk immunologi
Clinical Immunology

Added entries (persons, corporate bodies, meetings, titles ...)

Hedenstierna, GöranUppsala universitet,Klinisk fysiologi (thesis advisor)
Rylander, Christian,MD, PhDGöteborgs Universitet (thesis advisor)
Lindholm, Catharina,MD, PhDGöteborgs Universitet (thesis advisor)
Martijn, Cecile,PhDUppsala universitet,Institutionen för kemi - BMC (thesis advisor)
Annane, Djillali,MD, PhDUniversité de Versailles (opponent)
Uppsala universitetKlinisk fysiologi (creator_code:org_t)

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