Impact of age on the host response to sepsis in a murine model of fecal-induced peritonitis

Introduction Despite older adults being more vulnerable to sepsis, most preclinical research on sepsis has been conducted using young animals. This results in decreased scientific validity since age is an independent predictor of poor outcome. In this study, we explored the impact of aging on the ho...

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Published in:Intensive care medicine experimental 2024-03, Vol.12 (1), p.28-28, Article 28
Main Authors: Sharma, Neha, Chen, Alex, Heinen, Leah, Liu, Ruth, Dwivedi, Dhruva J., Zhou, Ji, Lalu, Manoj M., Mendelson, Asher A., McDonald, Braedon, Kretz, Colin A., Fox-Robichaud, Alison E., Liaw, Patricia C.
Format: Article
Language:English
Subjects:
Age
Critical Care Medicine
Fecal-induced peritonitis model
Feces
Immunothrombosis
Intensive
Intensive care
Medicine
Medicine & Public Health
Mortality
National Preclinical Sepsis Platform
Peritonitis
Sepsis
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Summary:Introduction Despite older adults being more vulnerable to sepsis, most preclinical research on sepsis has been conducted using young animals. This results in decreased scientific validity since age is an independent predictor of poor outcome. In this study, we explored the impact of aging on the host response to sepsis using the fecal-induced peritonitis (FIP) model developed by the National Preclinical Sepsis Platform (NPSP). Methods C57BL/6 mice (3 or 12 months old) were injected intraperitoneally with rat fecal slurry (0.75 mg/g) or a control vehicle. To investigate the early stage of sepsis, mice were culled at 4 h, 8 h, or 12 h to investigate disease severity, immunothrombosis biomarkers, and organ injury. Mice received buprenorphine at 4 h post-FIP. A separate cohort of FIP mice were studied for 72 h (with buprenorphine given at 4 h, 12 h, and then every 12 h post-FIP and antibiotics/fluids starting at 12 h post-FIP). Organs were harvested, plasma levels of Interleukin (IL)-6, IL-10, monocyte chemoattract protein (MCP-1)/CCL2, thrombin-antithrombin (TAT) complexes, cell-free DNA (CFDNA), and ADAMTS13 activity were quantified, and bacterial loads were measured. Results In the 12 h time course study, aged FIP mice demonstrated increased inflammation and injury to the lungs compared to young FIP mice. In the 72 h study, aged FIP mice exhibited a higher mortality rate (89%) compared to young FIP mice (42%) (p 
ISSN:2197-425X
2197-425X
DOI:10.1186/s40635-024-00609-8