Lay Summary

Proposal No.   IBD-0081R
Principal Investigator:  Martin J. Mangino, Ph.D.
Applicant Organization:   University of Wisconsin-Madison (U.S.A.)
Project Title:  Lipoxin metabolism in inflammatory bowel disease
Period of Award:  February 1, 2004 – April 30, 2006

Inflammatory bowel disease (IBD) is a chronic illness, which causes diarrhea, pain, weight loss, and malnutrition.  In severe cases, surgical removal of the intestine is required.  The body normally uses inflammatory reactions to destroy bacteria and injured tissue and to promote healing.  Chemical messengers secreted by white blood cells stimulate these inflammatory reactions.  Normally, these cells also release other chemicals that tell the white blood cells to stop the inflammatory reaction.

We propose that the uncontrolled inflammation in the intestine in IBD patients may be caused by inability of their tissues to secrete these chemical stop signals called lipoxins.  This could allow inflammation to run uncontrolled. We will test this idea by measuring these chemical stop signals in samples of intestine of patients with IBD.  We will also study the severity of IBD in mice genetically engineered to not make lipoxins.  If the IBD is more severe in these animals lacking lipoxins and if we can reverse the severe IBD by giving back stable lipoxins to the mice, then that will provide evidence that lipoxins indeed act as stop signals for inflammation during IBD.  These studies will also provide a rational reason for trying to enhance lipoxin synthesis in patients with IBD by using drugs with lipoxin stimulating effects.