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.

中文翻译：

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L-GILZ 转录变体 1 （GILZ TV 1） 的高表达与 30 天脓毒症死亡率增加相关，高表达比可能禁忌氢化可的松给药


脓毒症由于其复杂的免疫反应而面临挑战，其中炎症和抗炎之间的平衡对于生存至关重要。糖皮质激素诱导的亮氨酸拉链 （GILZ） 是实现这种平衡、抑制炎症和介导糖皮质激素反应的关键蛋白。本研究旨在调查脓毒症患者的 GILZ 转录本变异，并探索它们在患者分层和优化糖皮质激素治疗方面的潜力。符合脓毒症 3 中概述的标准的脓毒症患者被纳入，并从全血样本中分离 RNA。使用定量 PCR （qPCR） 评估脓毒症患者样本 （n = 121） 和单核细胞 U937 细胞系 （n = 3） 中 GILZ 转录变体的定量 mRNA 表达，用氢化可的松和脂多糖处理。GILZ 转录变体 1 （GILZ TV 1） 表达升高是脓毒症患者 30 天死亡率升高的标志物。脓毒症发作最初一天内 GILZ TV 1 水平升高与死亡率增加 2.2-[95% CI 1.2-4.3] 倍相关，到第 8 天增加到 8.5-[95% CI 2.0-36.4] 倍。细胞培养物中的糖皮质激素增强了 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 表达在脓毒症过程中和对氢化可的松治疗的反应中增加。此外，转录变体 1 相对于所有 GILZ mRNA TV 的高表达比与接受氢化可的松治疗的患者死亡率高 2.3 倍相关。GILZ TV 1 的高表达与较高的 30 天脓毒症死亡率相关。 此外，相对于所有 GILZ 转录变体，GILZ TV 1 的高表达比是识别可能禁忌氢化可的松的患者亚组的参数。