Glucocorticoid Receptor Expression in Peripheral WBCs of Critically Ill Children*

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.