Researchers discover new signaling pathway linked to inflammatory disease

December 14, 2010

Scientists at the University of California, San Diego School of Medicine have described for the first time a key inhibitory role for the IL-1 signaling pathway in the human innate immune system, providing novel insights into human inflammatory bowel disease (IBD) and potential new treatments.

The research, led by Jose M. Gonzalez-Navajas, PhD, and Eyal Raz, MD, a professor of medicine at UC San Diego, is published as a Brief Definitive Report in the December issue of The .

The researchers report that signaling by the interleukin 1 receptor (IL-1R) controls expression of a protein called DUBA (deubquitinase A), which in turn affects production of anti-inflammatory cytokines reacting to certain bacterial stimuli. Cytokines are molecules that help trigger an immune system response to infections and cancer. Some induce inflammation, some suppress it.

The IL-1R is essential to producing key anti-inflammatory cytokines like IL-10 and type 1 interferon, but , infection and some drugs can disrupt the signaling process, resulting in reduced or increased cytokine production that upsets delicate balances and leads to disease. Laboratory mice deficient in IL-1R type signaling were shown to produce fewer anti-inflammatory cytokines and were more susceptible to a condition similar to human . Human IBD encompasses a group of disorders affecting the colon and . The major types are Crohn's disease and ulcerative colitis.

The authors said the research also revealed the deleterious effects of some anti-inflammatory drugs. IL-1 is a pro-inflammatory cytokine implicated in certain conditions like rheumatoid arthritis and gout, the latter a painful inflammation of the toes and feet. The authors propose that several drugs currently used to treat these conditions by blocking IL-1 activity could be harmful to patients suffering from IBD, which generally involves an overwhelming immune response against normal, non-pathogenic gut bacteria.

"Our findings indicate that the use of such drugs can be harmful and therefore should be avoided in such patients," said Raz.

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