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

Microbes Infect. 2006 Mar;8(3):694-703. doi: 10.1016/j.micinf.2005.09.006. Epub 2006 Jan 13.


Th 1 cells activated by IL-12 and secreting IFN-gamma 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-gamma, 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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Chemokine CCL5 / metabolism
  • Colitis / genetics
  • Colitis / immunology*
  • Colitis / metabolism*
  • Colon / pathology
  • Feces / chemistry
  • Gene Expression Regulation
  • Immunoglobulin G / analysis
  • Inflammation / metabolism
  • Interleukin-10 / deficiency*
  • Interleukin-10 / genetics
  • Interleukin-4 / genetics
  • Interleukin-4 / metabolism*
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • RNA, Messenger / metabolism
  • Th1 Cells / metabolism
  • Th2 Cells / metabolism


  • Chemokine CCL5
  • Immunoglobulin G
  • RNA, Messenger
  • Interleukin-10
  • Interleukin-4