New signaling pathway linked to inflammatory disease discovered

WASHINGTON - Scientists 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 was led by Jose M. Gonzalez-Navajas and Eyal Raz, a professor of medicine at UC San Diego,

The researchers found 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 whereas some suppress it.

The IL-1R is essential to producing key anti-inflammatory cytokines like IL-10 and type 1 interferon, but genetic alterations, infection and some drugs can disrupt the signaling process, resulting in reduced or increased cytokine production that upsets delicate balances and leads to disease.

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.

The study has been published in The Journal of Experimental Medicine. (ANI)