Glucocorticoid receptor mRNA levels are selectively decreased in neutrophils of children with sepsisReportar como inadecuado




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Intensive Care Medicine

, Volume 35, Issue 7, pp 1247–1254

First Online: 17 April 2009Received: 19 May 2008Accepted: 22 February 2009

Abstract

ObjectiveCorticosteroids 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 designTwenty-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 resultsNeutrophils 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.

ConclusionsChildren 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.

KeywordsChildren Corticosteroids Cortisol sensitivity Sepsis Septic shock  Download fulltext PDF



Autor: Erica L. T. van den Akker - Jan W. Koper - Koen Joosten - Frank H. de Jong - Jan A. Hazelzet - Steven W. J. Lambert

Fuente: https://link.springer.com/







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