Research: Inflammatory bowel disease may be due to underactive immune system

28 February 2006

Might inflammatory bowel disease be due to an underactive rather than overactive immune system?

Inflammatory bowel disease (Crohn's disease) is widely thought to result from an autoimmune response inside the gut, triggered by an as yet unidentified pathogen. But the mechanism of disease has never been conclusively nailed down.

Professor Tony Segal and colleagues at University College London tested an alternative hypothesis: that it results from an impaired innate immune response. They found that damage to the skin, ileum or rectum of people with Crohn's disease, or injection of heat-killed E. coli, stimulated a relatively weak immune response.

The authors suggest that when such a response allows bowel contents to penetrate the gut's mucosal barrier, these are not then cleared from the bowel wall by an acute inflammatory response. The persistence of this foreign material leads to a secondary chronic inflammation, giving rise to the characteristic symptoms of Crohn's disease.

If confirmed, this would have major implications for treatment – which is currently aimed at inhibiting inflammatory responses. This may actually be further weakening the mucosal immune response, exacerbating chronic disease.

External links

• Marks DJ et al. Defective acute inflammation in Crohn's disease: a clinical investigation. Lancet 2006;367(9511):668–78.