title: Interleukin-10 gene-deficient mice develop a primary intestinal permeability defect in response to enteric microflora.
abstract: 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.
authors.affiliation: Department of Medicine, University of Alberta, Edmonton, Canada.
authors.forename: K L
authors.initials: KL
authors.lastname: Madsen
authors.forename: D
authors.initials: D
authors.lastname: Malfair
authors.forename: D
authors.initials: D
authors.lastname: Gray
authors.forename: J S
authors.initials: JS
authors.lastname: Doyle
authors.forename: L D
authors.initials: LD
authors.lastname: Jewell
authors.forename: R N
authors.initials: RN
authors.lastname: Fedorak
mesh_terms: D000818:Animals; D003106:Colon / Q000378:metabolism* / Q000382:microbiology / Q000473:pathology; D046508:Culture Techniques; D016207:Cytokines / Q000378:metabolism*; D005856:Germ-Free Life; D007082:Ileum / Q000378:metabolism* / Q000382:microbiology / Q000473:pathology; D015212:Inflammatory Bowel Diseases / Q000235:genetics* / Q000473:pathology; D016753:Interleukin-10 / Q000172:deficiency / Q000235:genetics*; D007413:Intestinal Mucosa / Q000378:metabolism* / Q000382:microbiology* / Q000473:pathology; D051379:Mice; D008815:Mice, Inbred Strains; D010539:Permeability; D012016:Reference Values; D012680:Sensitivity and Specificity
chemical_list: D016207:Cytokines; D016753:Interleukin-10