Lay Summary

Proposal No.  IBD-0154R
Principal Investigator:  Giovanni Monteleone, M.D., Ph.D.
Applicant Organization:  University Tor Vergata of Rome (Italy)
Project Title:  Interleukin-21 triggers inflammatory signals in the gut.  Relevance for human inflammatory bowel diseases.
Period of Award:  July 1, 2005 – June 30, 2007

The etiology of inflammatory bowel disease (IBD) is unknown, but evidence has been accumulated to show that the liability to develop Crohn’s disease (CD) or ulcerative colitis (UC) is influenced by a wide range of genetic and environmental factors. Some of these factors have been identified, but it is as yet unclear whether any single factor is essential for developing IBD. Whatever the complex genetic and environmental etiology of CD and UC, the unifying theme is that both diseases are caused by excessive immune reactivity in the gut wall.  Indeed, many treatment strategies for IBD patients are based on suppressing or modulating the immune system.  The challenge is to accomplish this in a targeted and specific way that is effective, but avoids systemic side-effects.  A major part of this effort involves clarification of the immune/inflammatory pathways in CD and UC to design disease-specific therapy.

We have recently shown that interleukin (IL)-21, a T cell-derived cytokine, is produced in excess in the inflamed gut of patients with both CD and UC, and that neutralization of IL-21 reduces the expression of inflammatory molecules which are associated with CD immune response.  Our preliminary data indicate also that IL-21 might modulate the activity of several cell types in the gut.  The proposed project is aimed at investigating whether IL-21 contributes to the tissue-damaging immune response in IBD, and whether blocking IL-21 may limit the ongoing inflammation in experimental models of IBD.