Elsevier

Microbes and Infection

Volume 8, Issue 3, March 2006, Pages 694-703
Microbes and Infection

Original article
Induction of chronic colitis in IL-10 deficient mice requires IL-4

https://doi.org/10.1016/j.micinf.2005.09.006Get rights and content
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Abstract

Th 1 cells activated by IL-12 and secreting IFN-γ have been described as the main mediators for onset and maintenance of chronic colitis in IL-10 deficient mice. It was therefore surprising that mice deficient for IL-4 in addition to IL-10 showed intestinal pathology very rarely, whereas IL-10 KO mice developed rectal prolapse in most cases. To investigate the underlying mechanisms, we studied changes of ongoing inflammatory processes in mice deficient for IL-4, IL-10 or both cytokines. Levels of IFN-γ, IL-12p40 and MHCII mRNA were elevated to a much higher degree in colonic tissue of IL-10 KO compared to IL-4/10 KO at the onset of colitis. Furthermore, the influx of eosinophils, a marker for Th2 responses, was investigated. Only IL-10 deficient mice displayed a significant increase of eosinophils in the lamina propria of the colon and rectum. In contrast, IL-4/10 deficient mice had eosinophil levels comparable to wildtype controls and IL-4 KO. Together these results indicate an important role of IL-4 for the onset of colitis in IL-10 KO mice by promoting a Th1 response and induction of a deleterious Th2 effector response.

Keywords

IL-10 KO mice
IL-4
Colitis
RANTES
Eosinophils

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