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Feb. 23, 2006 -- Researchers in the U.K. have a new theory to explain the cause of Crohn's disease, and they say medications like the erectile dysfunction drug Viagra may prove useful for treating the bowel disorder if they are right.

In Crohn's disease, chronic inflammation causes ulcers within the digestive tract that can lead to severe gastrointestinal symptoms, including abdominal pain, persistent diarrhea, and rectal bleeding.

The most widely accepted theory is that an overactive immune system causes the damaging inflammation. But researchers from the University College London say the opposite appears to be true.

They believe a weaker-than-normal immune response triggers the bowel inflammation that leads to Crohn's disease. Their research appears in the Feb. 25 issue of The Lancet.

1 Disease, 2 Theories

The prevailing theory of Crohn's disease is that the body's immune system reacts abnormally in people with the disorder, producing chronic inflammation that leads to bowel injury.

Tony Segal, professor of medicine at University College London, explains the weak immune system theory like this: "The wall of the bowel is normally an effective barrier against the bowel contents, but sometimes the barrier is broken by an infection or injury and the bowel contents, which include large numbers of bacteria, penetrate into the bowel wall.

"Normally, an acute inflammatory response would kick in to remove the bacteria and return the condition of the bowel to normal. But in Crohn's disease, we think that the acute inflammation fails to kick-start, leaving bacteria to fester in the bowel wall which, in turn, triggers chronic, secondary inflammations."

Segal and colleagues conducted a series of small experiments that measured white blood cell production in response to intestinal and skin trauma in both Crohn's patients and healthy patients. With inflammation, white blood cell numbers are expected to rise. In one experiment, researchers injected a killed gut bacteria into the forearms of patients and healthy participants to study blood flow and immune response.

They found that the Crohn's patients produced unexpectedly lower levels of white blood cells and proteins involved in inflammation, compared with people without the disorder.

Segal tells WebMD that people who carry a gene that has been linked to Crohn's disease may be especially vulnerable to getting the disease if they have weak immune systems.

He added that drugs like Viagra, which open the blood vessels and increase blood flow, may help.

The Viagra Response

The researchers tested this theory by treating 10 Crohn's patients with 50 milligrams of Viagra after injecting them with the killed gut bacteria. They found that blood flow to the infected area improved.

"Increasing blood flow is an important part of the inflammatory response, and that is why this drug may work," Segal says. "But we don't yet know if this will give rise to successful treatment. We need to study this further to find out."

Segal and colleagues are among a growing number of researchers suggesting that a weak immune system, rather than an overactive one, is largely responsible for Crohn's disease, says University of Chicago associate professor of medicine Sunanda Kane, MD.

She adds that the new research adds credibility to the theory but does not prove it.

"This is a little more evidence that maybe we have been barking up the wrong tree," she tells WebMD. "The idea that we should be strengthening the immune system -- rather than suppressing it -- sounded a little crazy at first, but the evidence continues to come in. But we still have a long way to go to really understand what causes Crohn's."

Biologic agents that stimulate a specific part of the immune system are now being tested in Crohn's patients. If such treatments prove effective, Kane says doctors would have an effective alternative to steroids, which work well for many patients but have many side effects.

"For decades now suppressing the immune system [with steroids] has worked, and we will continue to do so until we find alternatives that work for everybody and are risk-free," she says.