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Common Variables That Influence Sepsis Mortality in Mice.

Luiz F Garcia1, Vishwajeet Singh2, Blake Mireles3

  • 1Center of Emphasis in Infectious Diseases, Department of Molecular and Translational Medicine, Paul L. Foster School of Medicine, Texas Tech University Health Sciences Center El Paso, El Paso, TX, USA.

Journal of Inflammation Research
|March 21, 2023
PubMed
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Sepsis mortality in the cecal ligation and puncture (CLP) mouse model is influenced by sex and season. Factors like summer and delayed antibiotics impact males, while higher weight affects females, highlighting the need for careful study design.

Area of Science:

  • Sepsis research
  • Animal models of disease
  • Immunology

Background:

  • Sepsis involves a dysregulated immune response to infection, leading to organ dysfunction and high mortality.
  • The cecal ligation and puncture (CLP) mouse model is widely used for sepsis research.
  • Variability in mortality rates in CLP models can arise from unaddressed technical and animal factors, potentially biasing results.

Purpose of the Study:

  • To investigate the influence of mouse sex, age, weight, surgeon, season, and antibiotic timing on mortality in the CLP sepsis model.
  • To identify specific factors contributing to variability in sepsis outcomes within a standardized experimental setting.

Main Methods:

  • A comprehensive dataset of C57BL/6J mice undergoing CLP surgery between 2015-2020 was analyzed.
Keywords:
ageantibiotic timingcecal ligation and puncturemouseseasonsepsissexsurgeonvariablesweight

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  • Mortality was defined as time to death or study termination (14 days).
  • Log rank tests and Cox regression models were employed for statistical analysis.

    • Main Results:

    • Unadjusted analyses indicated that summer experiments and higher mouse weight predicted increased mortality.
    • In males, the summer season and delayed antibiotic administration were associated with higher mortality.
    • In females, higher weight significantly affected mortality, while delayed antibiotics increased mortality in non-summer seasons.

    Conclusions:

    • Sex and season-specific factors significantly influence sepsis mortality in the CLP mouse model.
    • Careful consideration of these variables, including appropriate group matching or adjusted analysis, is crucial for minimizing experimental variability.
    • These findings emphasize the importance of accounting for biological and environmental factors in sepsis research using the CLP model.