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Enterocolitis and colon cancer in interleukin-10-deficient mice are associated with aberrant cytokine production and CD4(+) TH1-like responses.
Open accessAbstract
We have characterized the progressive stages of chronic intestinal inflammation that develops spontaneously in specific pathogen-free (SPF) mice with a targeted disruption in the IL-10 gene (IL-10-/-). Our longitudinal studies showed that inflammatory changes first appear in the cecum, ascending and transverse colon of 3-wk-old mutants. As the disease progressed, lesions appeared in the remainder of the colon and in the rectum. Some aged IL-10-/- mice also developed inflammation in the small intestine. Prolonged disease with transmural lesions and a high incidence of colorectal adenocarcinomas (60%) was observed in 6-mo-old mutants. Mechanistic studies have associated uncontrolled cytokine production by activated macrophages and CD4+ Th1-like T cells with the enterocolitis exhibited by IL-10-/- mice. A major role for a pathogenic Th1 response was further suggested by showing that anti-IFNgamma antibody (Ab) treatment significantly attenuated intestinal inflammation in young IL-10-/- mice. When weanlings were treated with IL-10, they failed to develop any signs of intestinal inflammation. Interestingly, IL-10 treatment of adults was not curative but did ameliorate disease progression. Our studies have also shown that inheritable factors strongly influence the disease susceptibility of IL-10-/- mice. In 3-mo-old mutants, intestinal lesions were most severe in IL-10-/- 129/SvEv and IL-10-/- BALB/c strains, of intermediate severity in the IL-10-/- 129 x C57BL/6J outbreds, and least severe in the IL-10-/- C57BL/6J strain.
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“Interleukin-10-deficient (Il10-/-) mice develop chronic intestinal inflammation starting before three weeks of age when in contact with normal bacterial antigens and thereby mimic some features of CD.20,21 Onset, severity and site of the colitis are dependent on the genetic background of the mice and on the compositio…”
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Metadata
- Authors
- Berg, D. J., Davidson, N., Kühn, R., Müller, W., Menon, S., Holland, G., Thompson-Snipes, L., Leach, M. W., & Rennick, D.
- Venue
- Journal of Clinical Investigation
- Published
- 1996-08-15
- Volume
- 98
- Issue
- 4
- Pages
- 1010-1020
- ISSN
- 0021-9738 (ISSN-L)
- OpenAlex
- W2018075167
- Cited by
- 1,136
- References
- 3
- FWCI
- 17.25
- Type
- journal article
- Language
- en
- Open access
- bronze
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