ArticleIntensive care medicine2009
Glucocorticoid receptor mRNA levels are selectively decreased in neutrophils of children with sepsis.
Article in Intensive care medicine, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 34 papers.
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Who cites it
34 citing papers in PubMed, 80 citations in OpenAlex.
- The relationship between adrenocortical candidate gene expression and clinical response to hydrocortisone in patients with septic shock.Intensive care medicine · 2021Trial
- Critical illness-related corticosteroid insufficiency: latest pathophysiology and management guidelines.Acute and critical care · 2024Article
- Decreasing the steroid rapidly may help to improve the clinical outcomes of patients with intestinal steroid-refractory acute graft-versus-host disease receiving basiliximab treatment.Frontiers in oncology · 2024Article
- The Hypothalamus-pituitary-adrenocortical Response to Critical Illness: A Concept in Need of Revision.Endocrine reviews · 2023Article
- Theory and Practice of Glucocorticoids in COVID-19: Getting to the Heart of the Matter-A Critical Review and Viewpoints.Pharmaceuticals (Basel, Switzerland) · 2023Review
- Prenatal glucocorticoid administration accelerates the maturation of fetal rat hepatocytes.Molecular biology reports · 2022Article
- Critical Illness-induced Corticosteroid Insufficiency: What It Is Not and What It Could Be.The Journal of clinical endocrinology and metabolism · 2022Review
- Observational
- Impact of Hydrocortisone and of CRH Infusion on the Hypothalamus-Pituitary-Adrenocortical Axis of Septic Male Mice.Endocrinology · 2022Article
- Glucocorticoid Treatment Strategies in Liver Failure.Frontiers in immunology · 2022Review
- Restrained expression of canine glucocorticoid receptor splice variants α and P prognosticates fatal disease outcome in SIRS.Scientific reports · 2021Article
- Human DNA methylation signatures differentiate persistent from resolving MRSA bacteremia.Proceedings of the National Academy of Sciences of the United States of America · 2021Article
- Dysfunction of the hypothalamic-pituitary-adrenal axis in critical illness: a narrative review for emergency physicians.European journal of emergency medicine : official journal of the European Society for Emergency Medicine · 2020Review
- Glucocorticoid Receptor Polymorphisms in Children Undergoing Congenital Heart Surgery with Cardiopulmonary Bypass.Journal of pediatric intensive care · 2020Article
- Xenobiotic receptors in mediating the effect of sepsis on drug metabolism.Acta pharmaceutica Sinica. B · 2020Review
- General Adaptation in Critical Illness: Glucocorticoid Receptor-alpha Master Regulator of Homeostatic Corrections.Frontiers in endocrinology · 2020Review
- Glucocorticoids in Sepsis: To Be or Not to Be.Frontiers in immunology · 2020Review
- Adrenal function and dysfunction in critically ill patients.Nature reviews. Endocrinology · 2019Review
- How Glucocorticoids Affect the Neutrophil Life.International journal of molecular sciences · 2018Review
- Disease- and treatment-associated acquired glucocorticoid resistance.Endocrine connections · 2018Review
Corrections and comments
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Authors and funding
7 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
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-alpha (determining most of the cortisol effect), GR-P (increasing GR-alpha effect) and GR-beta (inhibitor of GR-alpha) were measured quantitatively. MAIN
resultsNeutrophils from sepsis patients showed decreased levels of glucocorticoid receptor mRNA of the GR-alpha and GR-P splice variants on day 0 compared to after recovery. GR-alpha and GR-P mRNA levels showed a gradual recovery on days 3 and 7 and normalized after recovery. GR-beta 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.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.