Adenosine Receptor Activation May Alleviate Inflammatory Bowel Disease

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Adenosine Receptor Activation May Alleviate Inflammatory Bowel Disease

NEW YORK (Reuters Health) Aug 18 - In animal models of inflammatory bowel disease (IBD), selective pharmacologic activation of the A2A adenosine receptor attenuates intestinal inflammation, largely by decreasing leukocyte infiltration and inhibiting proinflammatory cytokines, according to a report in the July issue of Gastroenterology.

Dr. Masaru Odashima from the University of Virginia Health System in Charlottesville and colleagues say activation of A2A by selective agonism may "serve as a novel therapy" for the treatment of IBD.

The adenosine A2A receptor uniquely induces anti-inflammatory signals upon activation and has previously been shown to attenuate ischemia/reperfusion injury of the heart, lung, liver, and kidney, the investigators point out.

To investigate the role of A2A in mucosal inflammation, Dr. Odashima's team administered ATL-146e, a selective A2A agonist, to experimental models of IBD.

They found, in a rabbit model of acute immune colitis, that ATL-146e administration significantly reduced the acute inflammatory index and tissue necrosis compared with vehicle administration. In a chronic immune colitis rabbit model, AT-146e significantly suppressed inflammatory cell infiltration into the colonic mucosa and prevented mortality.

Similar findings were achieved in a mouse model of spontaneous ileitis.

ATL-146e also suppressed interleukin-4 secretion. "This finding may be important in light of our recent data showing that this cytokine exerts proinflammatory effects during chronic small-intestinal inflammation," Dr. Odashima and colleagues note.

Taken together, the findings suggest that "acute and chronic intestinal inflammation represent additional targets for therapeutic administration of selective A2A receptor agonists," the researchers conclude.

Gastroenterol 2005;129:26-33.