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Effects of Early Initiation of High-Dose Dexamethasone Therapy on Pro-Inflammatory Cytokines and Mortality in LPS-Challenged Miceoa mark
  • Son, Ji Young ;
  • Kwack, Won Gun ;
  • Chung, Eun Kyoung ;
  • Shin, Sooyoung ;
  • Choi, Yeo Jin
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Publication Year
2022-07-01
Journal
Healthcare (Switzerland)
Publisher
MDPI
Citation
Healthcare (Switzerland), Vol.10 No.7
Keyword
acute inflammationcorticosteroiddexamethasonelipopolysaccharidesepsis
All Science Classification Codes (ASJC)
Leadership and ManagementHealth PolicyHealth InformaticsHealth Information Management
Abstract
This study aims to explore the effects of early dexamethasone therapy at low to high doses on the survival and inflammatory responses in lipopolysaccharide (LPS)-challenged mice. We performed two-series experiments to explore the impact of early dexamethasone therapy at different doses (0.5 mg/kg, 1.5 mg/kg, and 5 mg/kg; PO) on pro-inflammatory cytokine levels, including tumor necrosis factor-alpha (TNF-α) and interleukin-6 (IL-6), as well as survival in LPS-treated mice (10 mg/kg, IP). Dexamethasone was administered daily from 24 h before and 5 days after LPS challenge. Dose-dependent improved survival was demonstrated with dexamethasone (p < 0.05). Body weight was significantly decreased within 24 h of LPS injection, with significantly greater weight loss in the dexamethasone groups (p < 0.05). Weight changes were significantly associated with the days after LPS administration (p < 0.01), but not with the dexamethasone dose (p > 0.05). Mice treated with high-dose dexamethasone (5 mg/kg) had a significantly lowered serum TNF-α (134.41 ± 15.83 vs. 408.83 ± 18.32) and IL-6 (22.08 ± 4.34 vs. 91.27 ± 8.56) compared with those without dexamethasone. This study provides essential insights that the suppression of early-phase hyperactivation of pro-inflammatory activities through the early initiation of high-dose dexamethasone therapy increases sepsis-related prognosis.
ISSN
2227-9032
Language
eng
URI
https://aurora.ajou.ac.kr/handle/2018.oak/32803
https://www.scopus.com/inward/record.uri?partnerID=HzOxMe3b&scp=85133956574&origin=inward
DOI
https://doi.org/2-s2.0-85133956574
Journal URL
https://www.mdpi.com/2227-9032/10/7/1247/pdf?version=1656942967
Type
Article
Funding
Acknowledgments: This research was supported by a grant (no. 21153MFDS601-1) from the Ministry of Food and Drug Safety in 2021. This study was partially supported by a National Research Foundation of Korea (NRF) grant funded by the Ministry of Education in Korea (2021R1I1A1A01044500) and by the Ministry of Science and ICT (2021R1C1C1003735).Funding: This research was supported by a grant (No. 21153MFDS601-1) from the Ministry of Food and Drug Safety in 2021. This study was partially supported by a National Research Foundation of Korea (NRF) grant funded by the Ministry of Education in Korea (2021R1I1A1A01044500) and by the Ministry of Science and ICT (2021R1C1C1003735).
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Shin, Soo Young 신수영
Division of Pharmacy Sciences
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