Glucocorticoid receptor mRNA levels are selectively decreased in neutrophils of children with sepsis
Open Access
- 17 April 2009
- journal article
- research article
- Published by Springer Science and Business Media LLC in Intensive Care Medicine
- Vol. 35 (7), 1247-1254
- https://doi.org/10.1007/s00134-009-1468-6
Abstract
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. 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. 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). 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.This publication has 33 references indexed in Scilit:
- The human glucocorticoid receptor: One gene, multiple proteins and diverse responsesSteroids, 2005
- Expression of glucocorticoid receptors and in steroid sensitive and steroid insensitive interstitial lung diseasesThorax, 2004
- The Origin and Functions of Multiple Human Glucocorticoid Receptor IsoformsAnnals of the New York Academy of Sciences, 2004
- Role of the hypothalamic-pituitary-adrenal axis, glucocorticoids and glucocorticoid receptors in toxic sequelae of exposure to bacterial and viral productsJournal of Endocrinology, 2004
- Sepsis induces the transcription of the glucocorticoid receptor in skeletal muscle cellsClinical Science, 2003
- Serine-Arginine-rich Protein p30 Directs Alternative Splicing of Glucocorticoid Receptor Pre-mRNA to Glucocorticoid Receptor β in NeutrophilsOnline Journal of Public Health Informatics, 2003
- AUUUA motifs in the 3′UTR of human glucocorticoid receptor α and β mRNA destabilize mRNA and decrease receptor protein expressionSteroids, 2002
- Glucocorticoid Receptors Are Differentially Expressed in the Cells and Tissues of the Immune SystemCellular Immunology, 1998
- Glucocorticoid receptor beta, a potential endogenous inhibitor of glucocorticoid action in humans.JCI Insight, 1995
- Pediatric risk of mortality (PRISM) scoreCritical Care Medicine, 1988