Decreased Cytosolic Glucocorticoid Receptor Levels in Critically Ill Patients

Abstract

The immune system and the hypothalamic-pituitary-adrenal axis are linked by several mechanisms. Intracellular glucocorticoid receptors represent one important connection. The aim of this study was to examine the coherence between the number of glucocorticoid receptors, activation of the hypothalamic-pituitary-adrenal axis, inflammatory cytokine levels and the severity of illness in critically ill patients. In a prospective study, blood was collected from 20 healthy members of the hospital staff (control group) and 50 ventilated patients (sample group) within the first 24 hours after intubation and within three days of extubation. 3H-dexamethasone-binding assay was used to assess cytoplasmatic free glucocorticoid receptors levels. ACTH, cortisol, IL-6 and TNFa levels were measured by ELISA. In the sample group, specific binding of 3H-dexamethasone was significantly decreased compared to the control group. Glucocorticoid receptor levels tended to be lower in more severely ill patients. Plasma cortisol and ACTH levels were significantly different from the control group after extubation but not at intubation. Severe illness is associated with rapid down-regulation of 3H-dexamethasone binding. This decrease occurs before elevation of plasma cortisol. Therefore, down-regulation of cortisol binding may be directly associated with the stress response and not due to feedback regulation following increase in plasma cortisol levels.