Peritoneal wash contents used to predict mortality in a murine sepsis model

Joshua W. Kuethe, Emily F. Midura, Teresa C. Rice, Charles C. Caldwell

Research output: Contribution to journalArticlepeer-review

6 Scopus citations

Abstract

Background Cecal ligation and puncture (CLP) is considered the gold standard for inducing abdominal sepsis in mice. However, the model lacks source control, a component of sepsis management in humans. Using a CLP-excision model, we characterized peritoneal cytokines and cells and hypothesized these analyses would allow us to predict survival. Methods Fifty-eight mice were first subjected to CLP. Twenty hours later, the necrotic cecums were debrided, abdominal cavity lavaged, and intraperitoneal antibiotics administered. Peritoneal cytokines and leukocytes collected from the peritoneal lavage were analyzed. These immune parameters were used to generate receiver operator characteristic curves. In separate experiments, the accuracy of the model was verified with a survival cohort. Finally, we collected the peritoneal lavage and analyzed both serum and peritoneal cytokines, bacterial load, and leukocyte functionality. Results Peritoneal interleukin (IL)-6 levels and neutrophil CD11b intensity were observed to be significantly different in mice that lived versus those who died. In separate experiments, mice predicted to live (P-LIVE) had decreased bacterial loads, systemic IL-10, and neutrophil oxidative burst and increased peritoneal inflammatory monocyte numbers and phagocytosis. Conclusions This study couples a clinically relevant sepsis model with methodology to limit pathogen spread. Using surgical waste, stratification of the mice into groups P-LIVE and predicted to die was possible with a high degree of accuracy and specificity. In mice P-LIVE, increased inflammatory monocyte recruitment and phagocytosis were associated with decreased systemic IL-10 and bacterial loads.

Original languageEnglish (US)
Pages (from-to)211-219
Number of pages9
JournalJournal of Surgical Research
Volume199
Issue number1
DOIs
StatePublished - Nov 2015

Bibliographical note

Publisher Copyright:
© 2015 Elsevier Inc. All rights reserved.

Copyright:
Copyright 2016 Elsevier B.V., All rights reserved.

Keywords

  • Bacterial clearance
  • Cecal ligation and puncture
  • IL-6
  • Inflammation
  • Leukocyte
  • Neutrophil activation

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