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Glucocorticoid Receptor Expression in Peripheral WBCs of Critically Ill Children
Audrey R Ogawa Shibata1, Eduardo J Troster, Hector R Wong
11Pediatric Intensive Care Unit, Department of Pediatrics, Hospital Israelita Albert Einstein, Sao Paulo, Brazil. 2Division of Critical Care Medicine, Cincinnati Children's Hospital Medical Center and Cincinnati Children's Hospital Research Foundation, Cincinnati, OH.
Insights
Critically ill children with shock and severe illness show reduced glucocorticoid receptor expression in immune cells. Glucocorticoid receptor levels did not correlate with cortisol levels.
Area of Science:
- Pediatric critical care medicine
- Immunology
- Endocrinology
Background:
- Glucocorticoids are crucial for managing critically ill patients.
- Understanding glucocorticoid receptor (GR) expression is vital for optimizing treatment.
- Limited data exists on GR expression in pediatric critical illness.
Purpose of the Study:
- To quantify glucocorticoid receptor expression in peripheral white blood cells (WBCs) of critically ill children.
- To investigate the relationship between GR expression, illness severity, and cortisol levels.
Main Methods:
- Prospective observational cohort study in a tertiary pediatric intensive care unit (PICU).
- Flow cytometry used to measure GR expression on CD4 and CD8 lymphocytes.
- Parallel measurement of serum cortisol levels.
Main Results:
- Lower GR expression observed in CD4 and CD8 lymphocytes of children with cardiovascular failure compared to those without.
- Increased illness severity (high PRISM III scores, organ failure) correlated with reduced GR expression.
- No significant linear correlation found between cortisol concentrations and GR expression.
Conclusions:
- Critically ill children with shock and higher illness severity exhibit diminished GR expression in lymphocytes.
- Glucocorticoid receptor expression variability warrants further investigation in this population.
- Future research should explore strategies to enhance glucocorticoid responsiveness.
Objectives:
To characterize glucocorticoid receptor expression in peripheral WBCs of critically ill children using flow cytometry.
Design:
Prospective observational cohort.
Setting:
A university-affiliated, tertiary PICU.
Patients:
Fifty-two critically ill children.
Interventions:
Samples collected for measurement of glucocorticoid receptor expression and parallel cortisol levels.
Measurements And Main Results:
Subjects with cardiovascular failure had significantly lower glucocorticoid receptor expression both in CD4 lymphocytes (mean fluorescence intensity, 522 [354-787] vs 830 [511-1,219]; p = 0.036) and CD8 lymphocytes (mean fluorescence intensity, 686 [350-835] vs 946 [558-1,511]; p = 0.019) compared with subjects without cardiovascular failure. Subjects in the upper 50th percentile of Pediatric Risk of Mortality III scores and organ failure also had significantly lower glucocorticoid receptor expression in CD4 and CD8 lymphocytes. There was no linear correlation between cortisol concentrations and glucocorticoid receptor expression.
Conclusions:
Our study suggests that patients with shock and increased severity of illness have lower glucocorticoid receptor expression in CD4 and CD8 lymphocytes. Glucocorticoid receptor expression does not correlate well with cortisol levels. Future studies could focus on studying glucocorticoid receptor expression variability and isoform distribution in the pediatric critically ill population as well as on different strategies to optimize glucocorticoid response.
