Alimentary TractMice deficient in Th1- and Th2-type cytokines develop distinct forms of hapten-induced colitis☆,☆☆
Section snippets
Mice
Normal, IFN-γ gene–disrupted (IFN-γ−/−), IL-4 gene–disrupted (IL-4−/−), and IL-12 p40 gene–disrupted (IL-12−/−) mice, all of C57BL/6 background, and IL-12 p40 gene–disrupted (IL-12−/−) and IL-4−/− BALB/c mice were purchased from the Jackson Laboratory (Bar Harbor, ME). The mice were kept in microisolator cages in animal facilities at the Immunobiology Vaccine Center University of Alabama at Birmingham.
Induction of colitis
Mice were given a solution of TNBS (Research Organics, Cleveland, OH) dissolved in a mixture
Sensitivity of cytokine-deficient mice to TNBS colitis
For induction of TNBS colitis in cytokine gene–disrupted and control C57BL/6 (C57BL/6+/+) mice, we initially optimized the dose of hapten required to induce colitis. Both mortality and colitis in C57BL/6+/+ mice were dose dependent, and 40 μg/g body wt induced colitis with minimum death (Table 1).This dose was subsequently used in all experiments. Both IL-12−/− and C57BL/6+/+ mice showed similar degrees of survival after TNBS enema treatment, but IFN-γ−/− mice tended to be more resistant,
Acknowledgements
The authors thank Dr. Giorgio Trinchieri for providing hybridomas for anti–IL-12 monoclonal antibodies; Dr. Ed Leiter for discussions of this work and manuscript; Drs. Prosper N. Boyaka and John L. VanCott for lending their expertise with IL-12−/− and IFN-γ−/− mice; Drs. Casey Weaver and Audrey J. Lazenby for important discussions on histopathology of lesions; Dr. Raymond J. Jackson for help with the TGF-β assay; Annette M. Pitts for preparation of the tissues for histology; and Dr. Kim McGhee
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Address requests for reprints to: Taeko Dohi, M.D., Department of Gastroenterology, Research Institute, International Medical Center of Japan, 1-21-1 Toyama, Shinjuku-ku, Tokyo 162-8655, Japan. e-mail: [email protected]; fax: (81) 3-3202-7364.
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Supported by U.S. Public Health Service National Institutes of Health grants DK 44240, AI 18958, DE 09837, DE 12242, AI 43197, and AI 35932; and by a grant and contracts from Ministry of Education, Science, Sports and Cultures, the Ministry of Health and Welfare, and Organization for Pharmaceutical Safety and Research of Japan.