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 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.
Madsen
K L
KL
Department of Medicine, University of Alberta, Edmonton, Canada.
Malfair
D
D
Gray
D
D
Doyle
J S
JS
Jewell
L D
LD
Fedorak
R N
RN
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
D016207:Cytokines; D016753:Interleukin-10