Open AccessInterleukin‐10 gene‐deficient mice develop a primary intestinal permeability defect in response to enteric microflora
Author(s) -
Madsen Karen L.,
Malfair David,
Gray Derek,
Doyle Jason S.,
Jewell Laurence D.,
Fedorak Richard N.
Publication year - 1999
Publication title -
inflammatory bowel diseases
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.932
H-Index - 146
eISSN - 1536-4844
pISSN - 1078-0998
DOI - 10.1002/ibd.3780050405
Subject(s) - intestinal permeability , inflammation , tumor necrosis factor alpha , immune system , inflammatory bowel disease , cytokine , immunology , permeability (electromagnetism) , intestinal mucosa , interleukin 6 , medicine , pathology , biology , disease , biochemistry , membrane
The normal intestinal epithelium provides a barrier relatively impermeable to luminal constituents. However, patients with inflammatory bowel disease experience enhanced intestinal permeability that correlates with the degree of injury. IL‐10 gene‐deficient mice were studied to determine whether increased intestinal permeability occurs as a primary defect before the onset of mucosal inflammation or is secondary to mucosal injury. At 2 weeks of age, IL‐10 gene‐deficient mice show an increase in ileal and colonic permeability in the absence of any histological injury. This primary permeability defect is associated with increased mucosal secretion of interferon‐γ and tumor necrosis factor‐α, and does not involve an increase in nitric oxide synthase activity. Colonic permeability remains elevated as inflammation progresses, while ileal permeability normalizes by 6 weeks of age. IL‐10 gene‐deficient mice raised under germ‐free conditions have no inflammation, and demonstrate normal permeability and cytokine levels. This data suggests that the intestinal permeability defect in IL‐10 gene‐deficient mice occurs due to a dysregulated immune response to normal enteric microflora and, furthermore, this permeability defect exists prior to the development of mucosal inflammation.