• Stefan Rusev, Patrick Thon, Birte Dyck, Dominik Ziehe, Tim Rahmel, Britta Marko, Lars Palmowski, Hartmuth Nowak, Björn Ellger, Ulrich Limper, Elke Schwier, Dietrich Henzler, EhrentrautStefan FelixSFKlinik für Anästhesiologie und Operative Intensivmedizin, Universitätsklinikum Bonn, 53127, Bonn, Germany., Lars Bergmann, Matthias Unterberg, Michael Adamzik, Björn Koos, and Katharina Rump.
• Klinik für Anästhesiologie, Intensivmedizin und Schmerztherapie, Universitätsklinikum Knappschaftskrankenhaus Bochum, 44892, Bochum, Germany.
• Crit Care. 2024 Aug 12; 28 (1): 270270.

BackgroundSepsis 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.MethodsSepsis 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).ResultsElevated 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.ConclusionHigh 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.© 2024. The Author(s).

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