Lay Summary

Proposal No. IBD-0253
Principal Investigator: Bobby J. Cherayil, M.D.
Applicant Organization: Massachusetts General Hospital (Charlestown, U.S.A.)
Project Title: Iron-based modulation of cytokine biosynthesis for treatment of intestinal inflammation
Period of Award: November 1, 2008 – February 28, 2011 

Inflammatory bowel disease (IBD) is associated with disturbed absorption and recycling of iron, an essential nutrient that is required for various biological functions, including the production of red blood cells. Based on our current understanding of how iron is handled by the body, as well as evidence from clinical studies, these abnormalities are likely to be the result of an increase in the production of a liver hormone called hepcidin. The disturbance of iron handling in IBD manifests as anemia, a well-recognized problem in patients with the disease. Recent experiments carried out in our laboratory suggest that changes in iron distribution, specifically the sequestration of iron within macrophages that is caused by increased levels of hepcidin, may also contribute to the chronic intestinal inflammation of IBD. Thus, we speculate that blocking production of hepcidin may reduce the inflammation. This is a strategy that has never been tried before for the treatment of IBD. In the experiments proposed in this application, we will evaluate the usefulness of this new approach using mouse models of chronic intestinal inflammation to test the ability of hepcidin blocking compounds to reduce the severity of the inflammation. If our studies show that the strategy is effective, they could lead to the development of a whole new class of anti-inflammatory drugs for the treatment of IBD. Such drugs would have the added benefit of helping to correct the anemia that is associated with the disease.