Jiabao Li1, Miaorong Xie2, Yanan Yu3, Ziren Tang3, Chenchen Hang3, Chunsheng Li4. 1. Department of Critital Care Medicine, Beijing Friendship Hospital, Capital Medical University, No. 95 Yong'an Road, Xicheng District, Beijing 100050, China. 2. Emergency and Critical Care Center, Beijing Friendship Hospital, Capital Medical University, No. 95 Yong'an Road, Xicheng District, Beijing 100050, China. 3. Department of Emergency Medicine, Beijing Chaoyang Hospital, Capital Medical University, No. 8 Worker's Stadium South Road, Chaoyang District, Beijing 100020, China. 4. Emergency and Critical Care Center, Beijing Friendship Hospital, Capital Medical University, No. 95 Yong'an Road, Xicheng District, Beijing 100050, China. Electronic address: lcscyyy@163.com.
Abstract
PURPOSE: The study aimed to understand the molecular mechanisms that might lead to differences in the glucocorticoid response during sepsis. METHODS: Patients diagnosed with sepsis (n = 198) and 40 healthy controls were enrolled. Glucocorticoid receptor (GR) expression in circulating leukocytes and plasma levels of adrenocorticotropic hormone and cortisol on days 1 and 7 were measured in all participants. Expression profiling of 16 genes associated with GR expression in peripheral blood mononuclear cells (PBMCs) in 12 healthy controls and 26 patients with sepsis was performed by PCR. RESULTS: Cortisol levels were higher in patients with sepsis than in healthy controls on day 1 after admission and recovered to normal levels by day 7. GR expression was gradually downregulated in leukocyte subsets. Non-survivors showed lower GR and higher cortisol levels than survivors. GRα expression was lower in patients with sepsis than in controls, whereas GRβ showed the opposite trend. MicroRNAs related to GR resistance and suppression were altered in PBMCs during sepsis. CONCLUSION: Patients with sepsis showed upregulated plasma cortisol levels along with downregulated GR expression on various leukocyte subtypes, portending poor cortisol response and outcome. Changes in GR-regulatory miRNAs may be responsible for GR low expression.
PURPOSE: The study aimed to understand the molecular mechanisms that might lead to differences in the glucocorticoid response during sepsis. METHODS:Patients diagnosed with sepsis (n = 198) and 40 healthy controls were enrolled. Glucocorticoid receptor (GR) expression in circulating leukocytes and plasma levels of adrenocorticotropic hormone and cortisol on days 1 and 7 were measured in all participants. Expression profiling of 16 genes associated with GR expression in peripheral blood mononuclear cells (PBMCs) in 12 healthy controls and 26 patients with sepsis was performed by PCR. RESULTS:Cortisol levels were higher in patients with sepsis than in healthy controls on day 1 after admission and recovered to normal levels by day 7. GR expression was gradually downregulated in leukocyte subsets. Non-survivors showed lower GR and higher cortisol levels than survivors. GRα expression was lower in patients with sepsis than in controls, whereas GRβ showed the opposite trend. MicroRNAs related to GR resistance and suppression were altered in PBMCs during sepsis. CONCLUSION:Patients with sepsis showed upregulated plasma cortisol levels along with downregulated GR expression on various leukocyte subtypes, portending poor cortisol response and outcome. Changes in GR-regulatory miRNAs may be responsible for GR low expression.