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.
D J Berg, N Davidson, R Kühn, W Müller, S Menon, G Holland, L Thompson-Snipes, M W Leach, D Rennick
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---|---|---|
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J Lu, X Xu, Y Li, N Yu, Y Ding, Y Shi |
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IL-10-Dependent and -Independent Mechanisms Are Involved in the Cardiac Pathology Modulation Mediated by Fenofibrate in an Experimental Model of Chagas Heart Disease
J Rada, M Donato, FN Penas, CA Soto, ÁC Cevey, AV Pieralisi, R Gelpi, GA Mirkin, NB Goren |
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Y Gao, J Lu, C Zeng, J Yang, B Huang, N Zhang, L Li, X Fu |
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M Xie, J Yang, J Zhang, HL Sherman, Z Zhang, LM Minter, BD Hammock, Y Park, G Zhang |
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M Zurita-Turk, BM Souza, CP de Castro, VB Pereira, VP da Cunha, TM Preisser, AM de Faria, DC Machado, A Miyoshi |
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L Ma, W Shan, X Ding, P Yang, A Rozjan, Q Yao |
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S Kim, JY Lee, SG Shin, JK Kim, P Silwal, YJ Kim, NR Shin, PS Kim, M Won, SH Lee, SY Kim, M Sasai, M Yamamoto, JM Kim, JW Bae, EK Jo |
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2020 |