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Tumor necrosis factor-alpha mediates hyperglycemia-augmented gut barrier dysfunction in endotoxemia
Satoshi Yajima1, Hiroshi Morisaki, Ryohei Serita
1Departments of Anesthesiology, Keio University School of Medicine, Tokyo, Japan.
Critical Care Medicine
|February 25, 2009
Summary
Hyperglycemia worsens gut barrier dysfunction and bacterial spread in endotoxemia, with tumor necrosis factor-alpha (TNF-alpha) playing a key role. Inhibiting TNF-alpha improved gut barrier function in this animal study.
Area of Science:
- Gastroenterology
- Endocrinology
- Immunology
Background:
- Endotoxemia, a condition caused by bacterial endotoxins, can lead to gut barrier dysfunction.
- Hyperglycemia is increasingly recognized as a factor that may exacerbate inflammatory conditions.
Purpose of the Study:
- To investigate if hyperglycemia worsens gut barrier dysfunction and inflammation in endotoxemic rats.
- To determine the role of tumor necrosis factor-alpha (TNF-alpha) in hyperglycemia-associated gut mucosal permeability.
Main Methods:
- A prospective randomized animal study was conducted using male Wistar rats injected with lipopolysaccharide (LPS).
- Rats were allocated to receive normal saline, 40% glucose, or 10% glucose with insulin infusions.
- Measurements included blood glucose, insulin, cytokines, gut mucosal permeability, and bacterial translocation.
Main Results:
- Rats with hyperglycemia (over 400 mg/dL) showed significantly higher plasma dextran and TNF-alpha levels compared to normoglycemic groups.
- Increased bacterial translocation to mesenteric lymph nodes was observed in the hyperglycemic group.
- Inhibiting TNF-alpha converting enzyme restored gut mucosal permeability in hyperglycemic, endotoxemic rats.
Conclusions:
- Hyperglycemia exacerbates lipopolysaccharide-induced gut barrier dysfunction and bacterial translocation independently of insulin levels.
- Tumor necrosis factor-alpha (TNF-alpha) is a key mediator of gut mucosal dysfunction in endotoxemia associated with hyperglycemia.
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