New insight into cause of Crohn's disease

UK scientists have found evidence that suggests Crohn's disease is caused by a weak immune response. The researchers, who report their findings in an Article in this week's issue of The Lancet, also suggest that sildenafil (Viagra) might help in the treatment of the disease.

Crohn's disease is a chronic inflammatory disorder that causes ulcerations in the small and large intestines. Many scientists consider Crohn's to be an autoimmune disease--an illness that occurs when the body tissues are attacked by its own immune system. However, Anthony Segal (University College London, UK) and colleagues have found that, counter intuitively, the inflammation in Crohn's arises due to a weak immune response.

The investigators looked at the quantities of neutrophils (white blood cells) that patients with Crohn's disease produce in response to trauma at sites in the bowel (intestinal biopsy) and on the skin surface (skin abrasion). They found that in response to trauma, Crohn's disease patients produced much lower quantities of neutrophils and inflammatory mediators when compared with healthy individuals. Cultured blood cells were also abnormal in the patients. To test the inflammatory response to bacteria, the team also measured local inflammatory and blood flow changes in participants after injecting a harmless form of Escherichia Coli under their skin. In the healthy controls, blood flow in the area of inflammation increased approximately ten-fold by 24 hours. Crohn's disease patients, however, had much lower blood flow than controls. The researchers found that the abnormally low blood flow in Crohn's patients could be corrected by treatment with Viagra, indicating a possible role for the drug in the treatment of the disease.

The authors believe that in Crohn's disease, reduced or delayed recruitment of neutrophils to sites at which bacteria penetrate the intestinal wall might lead to the persistence of bacteria and other organic debris in the tissue. The body may respond to this build up of bacteria by secreting inflammatory molecules, which accumulate and lead to the development of chronic inflammation typical of Crohn's.

Professor Segal states: "Our investigations identified defective innate immunity in Crohn's disease…In Crohn's disease, a constitutionally weak immune response predisposes to accumulation of intestinal contents that breach the mucosal barrier of the bowel wall, resulting in granuloma formation and chronic inflammation."