First Department of Critical Care Medicine & Pulmonary Services, School of Medicine, National and Kapodistrian University of Athens, Evangelismos Hospital, Athens, Greece.
Biochemical Department, Evangelismos Hospital, Athens, Greece.
Front Endocrinol (Lausanne). 2024 Sep 9;15:1414785. doi: 10.3389/fendo.2024.1414785. eCollection 2024.
Critically ill patients, including those with brain injuries (BI), are frequently hospitalized in an intensive care unit (ICU). As with other critical states, an adequate stress response is essential for survival. Research on the hypothalamic-pituitary-adrenal gland (HPA) axis function in BI has primarily focused on assessing ACTH and cortisol levels. However, the immunological, metabolic, and hemodynamic effects of glucocorticoids (GCs) are mediated through the glucocorticoid receptor (GCR), a ubiquitously distributed intracellular receptor protein. Data on expression and its signaling in acute BI injury are lacking.
We designed a prospective observational study, carried out in one academic multi-disciplinary ICU. Forty-two critically ill patients with acute (BI)were included. These patients suffered from traumatic BI (N= 20), subarachnoid hemorrhage (N= 12), intracranial hemorrhage (N= 7), or ischemic stroke (N= 3). All patients were steroid-free. Twenty-four age and sex-matched healthy controls were used for comparison.
Expression of and the glucocorticoid-inducible leucine zipper (), serum cortisol, interleukins (IL) 6, 8, 10 and TNF- α, and the BI biomarkers glial fibrillary acidic protein (GFAP) and total Tau were measured on ICU admission (within 48 hours) and 5-7 days from admission. Compared to healthy controls, in the critically ill patients with BI, mRNA expression was significantly downregulated on admission, and after 5-7 days in the ICU (2.3-fold, p<0.05 and 2.6-fold, p<0.01, respectively). Even though was downregulated, its downstream gene, , was expressed at the same levels as in normal controls on admission and was significantly upregulated 5-7 days following admission (2-fold, p<0.001). TNF-α levels were undetectable at both time-points. expression levels inversely correlated with IL-6. The levels of cortisol and the BI biomarkers did not differ between the 2 time-points.
We provide novel evidence on the downregulated expression and upregulated signaling of the ligand-binding and functionally active GCR-α isoform in the polymorphonuclear neutrophils (PMNs) of critically ill patients with BI. The increased expression indicates an increased GC sensitivity in the PMNs of BI critically ill patients.
危重病患者，包括脑损伤（BI）患者，经常在重症监护病房（ICU）住院。与其他危急状态一样，适当的应激反应对于生存至关重要。关于 BI 下丘脑-垂体-肾上腺（HPA）轴功能的研究主要集中在评估 ACTH 和皮质醇水平上。然而，糖皮质激素（GCs）的免疫、代谢和血液动力学效应是通过糖皮质激素受体（GCR）介导的，GCR 是一种广泛分布的细胞内受体蛋白。关于急性 BI 损伤中 表达及其信号的资料尚缺乏。
我们设计了一项前瞻性观察性研究，在一个学术性多学科 ICU 进行。纳入 42 例急性（BI）危重病患者。这些患者患有创伤性 BI（N=20）、蛛网膜下腔出血（N=12）、颅内出血（N=7）或缺血性中风（N=3）。所有患者均未使用类固醇。使用 24 名年龄和性别匹配的健康对照进行比较。
在 ICU 入院时（48 小时内）和入院后 5-7 天，测量了 表达和糖皮质激素诱导的亮氨酸拉链（）、血清皮质醇、白细胞介素（IL）6、8、10 和 TNF-α以及 BI 生物标志物胶质纤维酸性蛋白（GFAP）和总 Tau。与健康对照组相比，BI 危重病患者入院时 mRNA 表达明显下调，入院后 5-7 天（2.3 倍，p<0.05 和 2.6 倍，p<0.01）。尽管 下调，但下游基因 以与正常对照组相同的水平表达，并在入院后 5-7 天明显上调（2 倍，p<0.001）。在这两个时间点均未检测到 TNF-α 水平。表达水平与 IL-6 呈负相关。皮质醇和 BI 生物标志物水平在这两个时间点没有差异。
我们提供了新的证据，证明 BI 危重病患者中性粒细胞（PMN）中配体结合和功能活性 GCR-α 同工型的表达下调和信号转导上调。PMN 中 的表达增加表明 BI 危重病患者 GC 敏感性增加。
