Scientists at the University of California, San Diego School of Medicine have described for the first time a key inhibitory（禁止的，抑制的） role for the IL-1 signaling pathway in the human innate¹（先天的，固有的） immune system, providing novel insights into human inflammatory bowel²（肠） 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 Definitive³ Report in the December issue of The Journal of Experimental Medicine.

The researchers report that signaling by the interleukin（白介素） 1 receptor (IL-1R) controls expression of a protein called DUBA (deubquitinase A), which in turn affects production of anti-inflammatory cytokines（细胞因子） reacting to certain bacterial⁴ stimuli⁵. Cytokines are molecules⁶ 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（干扰素） , but genetic⁷ alterations⁸, 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 deficient⁹ in IL-1R type signaling were shown to produce fewer anti-inflammatory cytokines and were more susceptible¹⁰ to a condition similar to human inflammatory bowel disease. Human IBD encompasses（包含，环绕） a group of disorders¹² affecting the colon¹³ and small intestine¹⁴（小肠） . The major types are Crohn's disease and ulcerative colitis（溃疡性结肠炎） .

The authors said the research also revealed the deleterious effects（有害影响） of some anti-inflammatory drugs. IL-1 is a pro-inflammatory cytokine implicated¹⁵ in certain conditions like rheumatoid arthritis¹⁶（风湿性关节炎） and gout（痛风） , 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 gut¹⁷ bacteria.

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