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Compartmentalization of tolerance to endotoxin
Catherine Fitting1, Suman Dhawan, Jean-Marc Cavaillon
1UP Cytokines and Inflammation, Institut Pasteur, Paris, France.
The Journal of Infectious Diseases
|March 20, 2004
Summary
This study establishes an ex vivo model to investigate endotoxin tolerance in mice. Results show immune cells develop tolerance to lipopolysaccharide (LPS) at different rates, with lung cells being less affected.
Area of Science:
- Immunology
- Cell Biology
- Sepsis Research
Background:
- Endotoxin tolerance is typically studied in vivo or in vitro.
- Sepsis patients exhibit ex vivo leukocyte hyporeactivity, termed endotoxin tolerance.
- An ex vivo model is needed to study this phenomenon.
Purpose of the Study:
- To establish an ex vivo model for analyzing endotoxin tolerance.
- To investigate the compartmentalized nature of endotoxin tolerance in mice.
- To compare tolerance development across different leukocyte populations.
Main Methods:
- Mice received intravenous lipopolysaccharide (LPS).
- Leukocytes from various compartments were isolated.
- Cells were challenged in vitro with LPS or Staphylococcus aureus Cowan I (SAC) to measure tumor necrosis factor (TNF) production.
Main Results:
- TNF production was detected in bronchoalveolar cells, peritoneal cells, splenocytes, and whole blood 1-3 hours post-LPS injection.
- Bone marrow cells did not produce TNF initially.
- Within 24 hours, most cell types showed reduced TNF production in response to LPS, indicating tolerance. Bronchoalveolar cells exhibited less tolerance.
- Tolerance kinetics and cross-tolerance with SAC varied by cell compartment.
Conclusions:
- Ex vivo endotoxin tolerance is compartmentalized.
- Bronchoalveolar cells are more resistant to developing endotoxin tolerance compared to splenocytes, peritoneal cells, and bone marrow cells.
- This ex vivo model provides insights into the differential immune responses in sepsis.