Abstract
Glucocorticoid (GC) therapy had been strongly recommended for pediatric sepsis (grade 1A). However, the recommendation was changed to grade 2C in 2020 due to weak evidence. About 32.8% of patients with pediatric septic develop relative adrenal insufficiency (RAI). But whether GC therapy should be determined by RAI status is controversial. This study utilized 21-day- old SF1CreSRBIfl/fl mice as the first pediatric RAI mouse model to assess the pathogenesis of RAI and evaluate GC therapy. RAI mice exhibited a substantially higher mortality rate in cecal ligation and puncture and cecal slurry–induced sepsis. These mice featured persistent inflammatory responses and were effectively rescued by GC therapy. RNA sequencing analysis revealed persistent inflammatory responses in RAI mice, caused by transcriptional dysregulation of AP-1 and NF-κB, and cytokine- induced secondary inflammatory response. Our findings support a precision medicine approach to guide GC therapy for pediatric patients based on the status of RAI.
Document Type
Article
Publication Date
4-2024
Digital Object Identifier (DOI)
https://doi.org/10.1093/infdis/jiad369
Funding Information
This work was supported by the National Institutes of Health (R01GM121796 and 1R35GM141478 to X.-A. L.; R01HL126795 to C. M.; R01HL131597 to P. W. S.).
Repository Citation
Hao, Dan; Guo, Ling; Wang, Qian; Ito, Misa; Huang, Bin; Mineo, Chieko; Shaul, Philip W.; and Li, Xiang-An, "Relative Adrenal Insufficiency Is a Risk Factor for Pediatric Sepsis: A Proof-of-Concept Study" (2024). Markey Cancer Center Faculty Publications. 255.
https://uknowledge.uky.edu/markey_facpub/255
Notes/Citation Information
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