Lack of interleukin-10 leads to intestinal inflammation, independent of the time at which luminal microbial colonization occurs
Version of Record online: 14 DEC 2006
Copyright © 2003 Crohn's & Colitis Foundation of America, Inc.
Inflammatory Bowel Diseases
Volume 9, Issue 2, pages 87–97, March 2003
How to Cite
Sydora, B. C., Tavernini, M. M., Wessler, A., Jewell, L. D. and Fedorak, R. N. (2003), Lack of interleukin-10 leads to intestinal inflammation, independent of the time at which luminal microbial colonization occurs. Inflamm Bowel Dis, 9: 87–97. doi: 10.1097/00054725-200303000-00002
- Issue online: 14 DEC 2006
- Version of Record online: 14 DEC 2006
- Manuscript Accepted: 18 NOV 2002
- Manuscript Received: 5 AUG 2002
- Crohn's and Colitis Foundation of Canada
- Inflammatory bowel disease;
- Crohn's disease
Previous studies have demonstrated that the resident bacteria harbored by interleukin (IL)-10 gene-deficient mice initiate an enterocolitis in the neonatal period. The associated intestinal injury is characterized by an increase in the secretion of interferon (IFN)-γ and tumor necrosis factor (TNF)-α, and by a systemic response to endogenous bacterial antigens, supporting the hypothesis that a lack of tolerance may be the initiating cause. Whether bacterial initiation of this enterocolitis would occur in the adult intestine or whether it is only seen in the developing neonatal intestine was not known. Adult (9 weeks of age), axenic, luminally sterile IL-10 gene-deficient mice, which do not spontaneously develop enterocolitis, were inoculated with intestinal microbial flora. These mice rapidly developed intestinal injury and demonstrated elevated levels of IFN-γ in cecal and colonic tissue. This response precedes a systemic spleen cell response to stimulation by bacterial antigens. Similarly, axenic, IL-10 gene-deficient mice exposed to microflora as neonates experience a comparable intestinal injury and IFN-γ release before the appearance of IFN-γ–producing cells in the spleen. Microbial colonization in control mice leads to systemic IL-10 production, but not systemic IFN-γ production, suggesting that an IL-10–mediated suppression regulates the response in normal control mice but is absent in IL-10 gene-deficient mice. Our results suggest that the point at which intestinal microbial colonization occurs does not significantly influence the severity or specificity of the inflammatory response in IL-10 gene-deficient mice. The lack of tolerance to bacterial antigens appears to result from the absence of IL-10 during bacterial exposure.