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Pro-inflammatory protein contributes to Crohn's disease according to UCSD School of Medicine study

A pro-inflammatory protein activated by bacteria in the colon plays a key role in the development of experimental colitis in mice a mouse-version of human Crohn's disease according to research by scientists at the University of California, San Diego (UCSD) School of Medicine.

The study, published in the February 4, 2005 issue of the journal Science, identified interleukin-1Beta (IL-1) as a major cause of severe inflammation in the mouse model of Crohn's disease, which is a painful, chronic and little-understood inflammatory bowel disease (IBD) in humans, affecting more than 500,000 Americans. These individuals are considered at high risk for colon cancer.

The identification of IL-1 offers a potential target for drug development, said the study's senior author, Michael Karin, Ph.D., UCSD professor of pharmacology and an American Cancer Society Research Professor. Although there is currently an IL-1 inhibitor on the market for other, non-Crohn's chronic inflammatory conditions such as rheumatoid arthritis, this drug is not a very potent IL-1 inhibitor.

"Now that we've identified IL-1 as an important target for Crohn's disease therapy, we hope that a better, more effective IL-1 inhibiting drug can be developed for testing its efficacy in these patients," Karin said.

Crohn's disease is thought to involve an interaction between a genetic defect and environmental factors such as bacterial infections that trigger the disorder. Recently, scientists identified mutations in a gene called NOD2 as leading to 50 percent of Crohn's cases in patients of Northern European descent, but they haven't known just how NOD2 causes the severe inflammation associated with the disorder. An intracellular sensor for bacterial infection, normal NOD2 activates a protein called nuclear factor-kappaB (NF-kB), which is involved in the immune system's rapid response to bacterial infection. It has been observed that many of the drugs currently used to help Crohn
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Contact: Sue Pondrom
spondrom@ucsd.edu
619-543-6163
University of California - San Diego
3-Feb-2005


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