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Updated: Jun 23, 2026

Colon Ascendens Stent Peritonitis (CASP) - a Standardized Model for Polymicrobial Abdominal Sepsis
Published on: December 18, 2010
Microbial tolerance in secondary peritonitis is dose dependent
Andreas M Lenz1, Matthias Turina, Pascale Alard
1Veterans Affairs Medical Center-Louisville, Louisville, KY 40206, USA.
Abstract:
Local microbial tolerance was investigated in a murine model of peritonitis. Peritoneal bacterial burden and inflammatory cytokine concentrations were determined at different times, within 48h after infection. Peritoneal macrophages were harvested from naïve mice or from mice 48h after infection and underwent ex vivo stimulation with different concentrations of Klebsiella. Cytokine secretion was determined in the supernatants. Peritoneal bacteria concentrations, remained relatively steady between 24h (median: 5.04 log CFU) and 48h (median: 5.19 log CFU) after infection. Peritoneal cytokine concentrations peaked early but were already diminished at 48h after infection, despite persistent high bacteria levels. Macrophages, harvested from naïve mice responded vigorously to ex vivo stimulation with 10(5) CFU and 2 x 10(8) CFU Klebsiella. Cells harvested from animals 48h after infection, were unresponsive to an ex vivo stimulation with 10(5) CFU Klebsiella, but fully responded to 10(8) CFU. Persistent intraabdominal bacterial infection induced dose dependent microbial tolerance in peritoneal macrophages.
Insights
Persistent abdominal bacterial infections can lead to microbial tolerance in peritoneal macrophages. This means immune cells become less responsive to pathogens over time, even with ongoing bacterial presence.
Area of Science:
- Microbiology
- Immunology
- Infectious Diseases
Background:
- Peritonitis involves bacterial infection within the abdominal cavity.
- Understanding the host's immune response, particularly macrophage function, is crucial for managing persistent infections.
Purpose of the Study:
- To investigate the development of local microbial tolerance in peritoneal macrophages during a murine model of peritonitis.
- To determine how bacterial burden and inflammatory cytokine levels change over time post-infection.
Main Methods:
- A murine model of peritonitis was established using Klebsiella.
- Peritoneal bacterial burden and cytokine concentrations were measured at various time points up to 48 hours.
- Peritoneal macrophages were isolated from infected and naive mice for ex vivo stimulation assays with varying Klebsiella concentrations.
Main Results:
- Bacterial concentrations in the peritoneum remained stable between 24 and 48 hours post-infection.
- Inflammatory cytokine levels peaked early and decreased by 48 hours, despite persistent bacteria.
- Macrophages from infected mice showed reduced responsiveness to low-dose Klebsiella stimulation but responded to high doses, indicating dose-dependent tolerance.
Conclusions:
- Persistent intra-abdominal bacterial infection induces dose-dependent microbial tolerance in peritoneal macrophages.
- This tolerance may impair the immune system's ability to clear the infection effectively.
- Further research is needed to understand the mechanisms and implications of this phenomenon.
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