Journal article
Enterocolitis and colon cancer in interleukin-10-deficient mice are associated with aberrant cytokine production and CD4(+) TH1-like responses
The Journal of clinical investigation, Vol.98(4), pp.1010-1020
08/15/1996
DOI: 10.1172/JCI118861
PMCID: PMC507517
PMID: 8770874
Abstract
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.
Details
- Title: Subtitle
- Enterocolitis and colon cancer in interleukin-10-deficient mice are associated with aberrant cytokine production and CD4(+) TH1-like responses
- Creators
- Daniel J Berg - Department of Immunology and Molecular Biology, DNAX Research Institute of Cellular and Molecular Biology, Palo Alto, California 94304, USANatalie Davidson - Department of Immunology and Molecular Biology, DNAX Research Institute of Cellular and Molecular Biology, Palo Alto, California 94304, USARalf Kühn - Department of Immunology and Molecular Biology, DNAX Research Institute of Cellular and Molecular Biology, Palo Alto, California 94304, USAWerner Müller - Department of Immunology and Molecular Biology, DNAX Research Institute of Cellular and Molecular Biology, Palo Alto, California 94304, USASatish Menon - Department of Immunology and Molecular Biology, DNAX Research Institute of Cellular and Molecular Biology, Palo Alto, California 94304, USAGina Holland - Department of Immunology and Molecular Biology, DNAX Research Institute of Cellular and Molecular Biology, Palo Alto, California 94304, USALuAnn Thompson-Snipes - Department of Immunology and Molecular Biology, DNAX Research Institute of Cellular and Molecular Biology, Palo Alto, California 94304, USAMichael W Leach - Department of Immunology and Molecular Biology, DNAX Research Institute of Cellular and Molecular Biology, Palo Alto, California 94304, USADonna Rennick - Department of Immunology and Molecular Biology, DNAX Research Institute of Cellular and Molecular Biology, Palo Alto, California 94304, USA
- Resource Type
- Journal article
- Publication Details
- The Journal of clinical investigation, Vol.98(4), pp.1010-1020
- DOI
- 10.1172/JCI118861
- PMID
- 8770874
- PMCID
- PMC507517
- ISSN
- 0021-9738
- eISSN
- 1558-8238
- Language
- English
- Date published
- 08/15/1996
- Academic Unit
- Hematology, Oncology, and Blood & Marrow Transplantation; Internal Medicine
- Record Identifier
- 9984094370802771
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