http://www.newscientist.com/channel/health/dn8759.html

Weak immune response may cause Crohn's disease

11:30 24 February 2006
NewScientist.com news service
Lisa Hitchen


Crohn’s disease might be due to a weak immune response, contrary to current thinking, suggests research by UK scientists. They also suggest that Viagra might help treat the disease by increasing blood flow and enhancing the body's immune response.

Crohn’s disease is a long term, inflammatory condition that leads to holes and ulcers in the small and large intestines and can severely impact on sufferers’ quality of life. Its cause has remained a mystery but current thinking is that it is an autoimmune disorder; where the body attacks its own tissues.

But a team from University College London, UK, wondered if the disorder might be due to an under reaction of the immune system instead.

A lack of an acute inflammatory response might lead to the delay or incomplete removal of bacteria and other bowel contents from the gut characterised by Crohn’s. This material then breaches the mucosal barrier, and its continued presence might provoke a huge immune reaction and secondary chronic inflammation, the researchers reasoned.

White blood cells
The team compared patients with Crohn’s disease with matched healthy controls. They took a sample from the rectums of nine controls and six patients to see the gut’s reaction to the scraping.

The mucosa (or membrane) was normal in all patients at the start, but six hours after the biopsy, healthy controls had an acute inflammatory response but the patients with Crohn’s did not. They produced much lower amounts of white blood cells and inflammatory mediators – with a 79% reduction in immune cells called neutrophils and a 63% reduction in interleukin 8-positive cells, in comparison with controls. Research on the small intestine gave a similar result.

To check whether the response was just confined to the gut, the team did another experiment using sandpaper to breach the skin barrier. Five hours after this trauma, 13 Crohn’s patients still had much lower numbers of neutrophils and interleukin 8 cells at the trauma site than controls.

Dead E. coli
Further experiments injecting heat-killed Escherichia coli into the skin on the forearm lead to a nine-fold increase in blood flow to the trauma site in healthy controls 24 hours later, but not in the 12 Crohn’s patients tested.

“In Crohn’s patients this was grossly defective,” Anthony Segal, who led the study, told New Scientist. The researchers then tested Viagra (sildenafil) to see its effect on blood flow.

“This resulted in marked increases in blood flow in all patients so it might be helpful in treatment of Crohn’s, particularly in the colon,” says Segal. He says his team are the first to trial use of Viagra for patients with Crohn’s disease. The study was self-funded, he notes.

Journal reference: The Lancet (vol 367 p 668)