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

Inflamm Bowel Dis. 1999 Nov;5(4):262-70. doi: 10.1097/00054725-199911000-00004.


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-gamma and tumor necrosis factor-alpha, 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.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Colon / metabolism*
  • Colon / microbiology
  • Colon / pathology
  • Culture Techniques
  • Cytokines / metabolism*
  • Germ-Free Life
  • Ileum / metabolism*
  • Ileum / microbiology
  • Ileum / pathology
  • Inflammatory Bowel Diseases / genetics*
  • Inflammatory Bowel Diseases / pathology
  • Interleukin-10 / deficiency
  • Interleukin-10 / genetics*
  • Intestinal Mucosa / metabolism*
  • Intestinal Mucosa / microbiology*
  • Intestinal Mucosa / pathology
  • Mice
  • Mice, Inbred Strains
  • Permeability
  • Reference Values
  • Sensitivity and Specificity


  • Cytokines
  • Interleukin-10