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Open Access 01-07-2009 | Original

Glucocorticoid receptor mRNA levels are selectively decreased in neutrophils of children with sepsis

Authors: Erica L. T. van den Akker, Jan W. Koper, Koen Joosten, Frank H. de Jong, Jan A. Hazelzet, Steven W. J. Lamberts, Anita C. S. Hokken-Koelega

Published in: Intensive Care Medicine | Issue 7/2009

Abstract

Objective

Corticosteroids are used in sepsis treatment to benefit outcome. However, discussion remains on which patients will benefit from treatment. Inter-individual variations in cortisol sensitivity, mediated through the glucocorticoid receptor, might play a role in the observed differences. Our aim was to study changes in mRNA levels of three glucocorticoid receptor splice variants in neutrophils of children with sepsis.

Patients and design

Twenty-three children admitted to the pediatric intensive care unit with sepsis or septic shock were included. Neutrophils were isolated at days 0, 3 and 7, and after recovery (>3 months). mRNA levels of the glucocorticoid receptor splice variants GR-α (determining most of the cortisol effect), GR-P (increasing GR-α effect) and GR-β (inhibitor of GR-α) were measured quantitatively.

Main results

Neutrophils from sepsis patients showed decreased levels of glucocorticoid receptor mRNA of the GR-α and GR-P splice variants on day 0 compared to after recovery. GR-α and GR-P mRNA levels showed a gradual recovery on days 3 and 7 and normalized after recovery. GR-β mRNA levels did not change significantly during sepsis. GR expression was negatively correlated to interleukin-6 (a measure of disease severity, r = −0.60, P = 0.009).

Conclusions

Children with sepsis or septic shock showed a transient depression of glucocorticoid receptor mRNA in their neutrophils. This feature may represent a tissue-specific adaptation during sepsis leading to increased cortisol resistance of neutrophils. Our study adds to understanding the mechanism of cortisol sensitivity in immune cells. Future treatment strategies, aiming at timing and tissue specific regulation of glucocorticoids, might benefit patients with sepsis or septic shock.

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Title: Glucocorticoid receptor mRNA levels are selectively decreased in neutrophils of children with sepsis
Authors: Erica L. T. van den Akker
Jan W. Koper
Koen Joosten
Frank H. de Jong
Jan A. Hazelzet
Steven W. J. Lamberts
Anita C. S. Hokken-Koelega
Publication date: 01-07-2009
Publisher: Springer-Verlag
Published in: Intensive Care Medicine / Issue 7/2009
Print ISSN: 0342-4642
Electronic ISSN: 1432-1238
DOI: https://doi.org/10.1007/s00134-009-1468-6

At a glance: The ONWARDS insulin icodec trials

Springer Medicine

Glucocorticoid receptor mRNA levels are selectively decreased in neutrophils of children with sepsis

Abstract

Objective

Patients and design

Main results

Conclusions

At a glance: The ONWARDS insulin icodec trials

Springer Medicine

Abstract

Objective

Patients and design

Main results

Conclusions

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