Interleukin-10 gene-deficient mice develop a primary intestinal permeability defect in response to enteric microflora

KL Madsen, D Malfair, D Gray, JS Doyle… - Inflammatory bowel …, 1999 - academic.oup.com
KL Madsen, D Malfair, D Gray, JS Doyle, LD Jewell, RN Fedorak
Inflammatory bowel diseases, 1999academic.oup.com
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 …
Summary
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.
Oxford University Press