Supported by the Spanish Ministry of Science and Innovation (SAF2008-02616), and the Junta de Andalucia (CTS 164). M Comalada is a recipient of the “Ramon y Cajal” Program, Spanish Ministry of Science and Innovation; N. Garrido-Mesa and M. Cueto-Sola are predoctoral fellows of the Spanish Ministry of Science and Innovation. CIBERehd is funded by the Instituto de Salud Carlos III.
DNFB-DNS hapten-induced colitis in mice should not be considered a model of inflammatory bowel disease†
Article first published online: 22 DEC 2010
Copyright © 2010 Crohn's & Colitis Foundation of America, Inc.
Inflammatory Bowel Diseases
Volume 17, Issue 10, pages 2087–2101, October 2011
How to Cite
Bailón, E., Cueto-Sola, M., Utrilla, P., Nieto, A., Garrido-Mesa, N., Celada, A., Zarzuelo, A., Xaus, J., Gálvez, J. and Comalada, M. (2011), DNFB-DNS hapten-induced colitis in mice should not be considered a model of inflammatory bowel disease. Inflamm Bowel Dis, 17: 2087–2101. doi: 10.1002/ibd.21586
- Issue published online: 11 SEP 2011
- Article first published online: 22 DEC 2010
- Manuscript Received: 27 OCT 2010
- Manuscript Accepted: 27 OCT 2010
- intestinal inflammation;
- irritable bowel syndrome;
- contact hypersensitivity;
- food allergy;
- TNBS colitis model
The dinitrofluorobenzene/dinitrosulfonic acid (DNFB/DNS) model was originally described as an experimental model of intestinal inflammation resembling human ulcerative colitis (UC). Due to the absence of acceptable UC experimental models for pharmacological preclinical assays, here we examine the immune response induced in this model.
Balb/c mice were sensitized by skin application of DNFB on day 1, followed by an intrarectal challenge with DNS on day 5. We further expanded this model by administering a second DNS challenge on day 15. The features of colonic inflammation and immune response were evaluated.
The changes observed in colonic tissue corresponded, in comparison to the trinitrobenzene sulfonic acid (TNBS) colitis model, to a mild mucosal effect in the colon, which spontaneously resolved in less than 5 days. Furthermore, the second hapten challenge did not exacerbate the inflammatory response. In contrast to other studies, we did not observe any clear involvement of tumor necrosis factor alpha (TNF-α) or other Th1 cytokines during the initial inflammatory response; however, we found that a more Th2-humoral response appeared to mediate the first contact with the hapten. An increased humoral response was detected during the second challenge, although an increased Th1/Th17-cytokine expression profile was also simultaneously observed.
On the basis of these results, although the DNFB/DNS model can display some features found in human UC, it should be considered as a model for the study of the intestinal hypersensitivity seen, for example, during food allergy or irritable bowel syndrome but not intestinal inflammation per se. (Inflamm Bowel Dis 2011;)