Klinik für Anästhesiologie, Intensivmedizin und Schmerztherapie, Universitätsklinikum Knappschaftskrankenhaus Bochum, 44892, Bochum, Germany.
Center for Artificial Intelligence, Medical Informatics and Data Science, University Hospital Knappschaftskrankenhaus Bochum, 44892, Bochum, Germany.
Crit Care. 2024 Aug 12;28(1):270. doi: 10.1186/s13054-024-05056-1.
Sepsis presents a challenge due to its complex immune responses, where balance between inflammation and anti-inflammation is critical for survival. Glucocorticoid-induced leucine zipper (GILZ) is key protein in achieving this balance, suppressing inflammation and mediating glucocorticoid response. This study aims to investigate GILZ transcript variants in sepsis patients and explore their potential for patient stratification and optimizing glucocorticoid therapy.
Sepsis patients meeting the criteria outlined in Sepsis-3 were enrolled, and RNA was isolated from whole blood samples. Quantitative mRNA expression of GILZ transcript variants in both sepsis patient samples (n = 121) and the monocytic U937 cell line (n = 3), treated with hydrocortisone and lipopolysaccharides, was assessed using quantitative PCR (qPCR).
Elevated expression of GILZ transcript variant 1 (GILZ TV 1) serves as a marker for heightened 30-day mortality in septic patients. Increased levels of GILZ TV 1 within the initial day of sepsis onset are associated with a 2.2-[95% CI 1.2-4.3] fold rise in mortality, escalating to an 8.5-[95% CI 2.0-36.4] fold increase by day eight. GILZ TV1 expression is enhanced by glucocorticoids in cell culture but remains unaffected by inflammatory stimuli such as LPS. In septic patients, GILZ TV 1 expression increases over the course of sepsis and in response to hydrocortisone treatment. Furthermore, a high expression ratio of transcript variant 1 relative to all GILZ mRNA TVs correlates with a 2.3-fold higher mortality rate in patients receiving hydrocortisone treatment.
High expression of GILZ TV 1 is associated with a higher 30-day sepsis mortality rate. Moreover, a high expression ratio of GILZ TV 1 relative to all GILZ transcript variants is a parameter for identifying patient subgroups in which hydrocortisone may be contraindicated.
脓毒症的免疫反应复杂，炎症和抗炎反应之间的平衡对患者的生存至关重要。糖皮质激素诱导亮氨酸拉链（GILZ）是实现这种平衡的关键蛋白，可抑制炎症并介导糖皮质激素反应。本研究旨在探讨脓毒症患者中 GILZ 转录变体，并探索其在患者分层和优化糖皮质激素治疗中的潜在应用。
符合 Sepsis-3 标准的脓毒症患者入选本研究，采集全血样本并提取 RNA。采用实时定量 PCR（qPCR）检测脓毒症患者（n=121）和单核细胞 U937 细胞系（n=3）经地塞米松和脂多糖处理后 GILZ 转录变体的定量 mRNA 表达。
GILZ 转录变体 1（GILZ TV 1）的高表达可作为脓毒症患者 30 天死亡率升高的标志物。脓毒症发病初期 GILZ TV 1 水平升高与死亡率升高 2.2 倍（95%CI 1.2-4.3）相关，发病第 8 天死亡率升高 8.5 倍（95%CI 2.0-36.4）。细胞培养中糖皮质激素可增强 GILZ TV1 的表达，但不受 LPS 等炎症刺激的影响。在脓毒症患者中，GILZ TV 1 的表达在脓毒症过程中逐渐增加，并对氢化可的松治疗产生反应。此外，在接受氢化可的松治疗的患者中，GILZ TV 1 相对于所有 GILZ mRNA TVs 的表达比值与死亡率升高 2.3 倍相关。
GILZ TV 1 的高表达与脓毒症 30 天死亡率升高相关。此外，GILZ TV 1 相对于所有 GILZ 转录变体的表达比值是识别氢化可的松可能禁忌的患者亚组的参数。
