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

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 inc reased intestinal permeability occurs as a primary defect before the onset of mucosal inflammation or is secondary to mucosal injury. At 2 weeks of ag e, IL-10 gene-deficient mice show an increase in ileal and colonic permeabi lity in the absence of any histological injury. This primary permeability d efect is associated with increased mucosal secretion of interferon-gamma an d tumor necrosis factor-alpha, and does not involve an increase in nitric o xide synthase activity. Colonic permeability remains elevated as inflammati on 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 sugges ts that the intestinal permeability defect in IL-10 gene-deficient mice occ urs due to a dysregulated immune response to normal enteric microflora and, furthermore, this permeability defect exists prior to the development of m ucosal inflammation.