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.

中文翻译：

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败血症早期白细胞糖皮质激素受体表达及相关转录组基因特征

目的

该研究旨在了解可能导致败血症期间糖皮质激素反应差异的分子机制。

方法

入选诊断为败血症的患者（n = 198）和40名健康对照。在所有参与者中，在第1天和第7天测量了循环白细胞中糖皮质激素受体（GR）的表达以及促肾上腺皮质激素和皮质醇的血浆水平。通过PCR进行了12个健康对照和26名脓毒症患者外周血单个核细胞（PBMC）中与GR表达相关的16个基因的表达谱分析。

结果

败血症患者入院后第1天皮质醇水平高于健康对照组，到第7天恢复到正常水平。白细胞亚群中GR表达逐渐下调。非幸存者的GR和皮质醇水平低于幸存者。脓毒症患者的GRα表达低于对照组，而GRβ显示相反的趋势。在脓毒症期间，PBMC中与GR抗性和抑制相关的MicroRNA发生了变化。

结论

败血症患者在各种白细胞亚型中血浆皮质醇水平升高，而GR表达下调，预示皮质醇反应和预后不良。GR调节miRNA的变化可能是GR低表达的原因。