TITLE

Inflammatory bowel disease: lessons from the IL-10 gene-deficient mouse

AUTHOR(S)
Madsen, Karen L.; Madsen, K L
PUB. DATE
October 2001
SOURCE
Clinical & Investigative Medicine;Oct2001, Vol. 24 Issue 5, p250
SOURCE TYPE
Academic Journal
DOC. TYPE
journal article
ABSTRACT
The pathogenesis of Crohn's disease likely involves multifactorial interactions between genetic factors and environmental triggers. The most recent studies suggest that luminal bacteria are a significant factor in the onset and chronicity of inflammation. In interleukin-10 (IL-10) gene-deficient mice a Crohn's-like colitis develops when the mice are raised under conventional animal care facilities but fails to develop when they are raised under germ-free conditions. These mice demonstrate significant alterations in the species and the levels of bacteria colonizing the colon, suggesting that genetic factors in the host may be critical in controlling bacterial colonization. In addition, early treatment of IL-10 gene-deficient mice with antibiotics can prevent the development of colitis in later life, suggesting that early events during the neonatal period can influence later disease progression. Recent work has focused on using probiotic bacterial mixtures to alter the microbial balance in the colon in attempts to reduce inflammation. The use of the VSL-3 probiotic mixture in the IL-10 gene-deficient mouse resulted in a complete normalization of physiological transport function and barrier integrity, in conjunction with a reduction in mucosal secretion of TNF-alpha and IFN-gamma. Further, it would appear that a soluble factor is released from a bacterium found in the VSL-3 mixture that can act directly on the epithelium to enhance barrier integrity. Results from animal models of inflammatory bowel disease suggest that genetically susceptible hosts can mount a pathogenic cellular immune response to specific nonpathogenic bacterial species, as a consequence of defective immunologic tolerance and lack of appropriate mucosal defences. Probiotic bacteria appear to be a promising new alternative for the treatment of clinical conditions that are associated with alterations in gut barrier function, including Crohn' s disease. INSET: The Joe Doupe Young Investigator's Award.
ACCESSION #
5334182

 

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