Weakened Immune System May Cause Crohn's Disease

Finding runs counter to conventional wisdom, and researchers found Viagra helped

THURSDAY, Feb. 23, 2006 (HealthDay News) -- A weak immune system, rather than an overactive one, may be responsible for Crohn's disease, a new study reports.

Even more surprising, the researchers also believe Viagra may aid in the treatment of Crohn's by restoring normal blood flow to the intestines.

"When you see a patient with Crohn's, you find they have a lot of inflammation, so it's been assumed that they have a hyper-inflammatory response," said Dr. Anthony W. Segal, a professor of medicine at University College London. "But we believe that the underlying problem is not hyper[activity], but failure of the acute inflammatory response."

Segal is the senior author of a paper detailing the findings in the Feb. 25 issue of The Lancet.

But others feel that the work does not really break new ground. "There have been other studies in the last year or two that Crohn's disease is really a problem dealing with bacteria in the colon and the inflammation is set up because there's more of a defective immune response to the bacteria in the gut," said Dr. John Thompson, director of the division of pediatric gastroenterology and nutrition at the University of Miami's Miller School of Medicine.

People with Crohn's disease have chronic inflammation, usually of the small intestine, which results in pain and diarrhea.

Many experts believe that disease flare-ups are caused when immune system cells release excess amounts of molecules called cytokines, which attack the intestinal cells and cause the inflammation.

The actual cause of the disorder remains unknown.

These British researchers investigated the possibility that immunodeficiency might be at the root of the problem.

Segal and his colleagues measured the number of neutrophils (white blood cells) produced by Crohn's patients in response to trauma in the bowel and on the surface of the skin.

Surprisingly, these patients produced 79 percent fewer neutrophils and inflammatory mediators compared with healthy individuals subjected to the same trauma.

When a harmless form of bacteria was injected under the skin, blood flow in healthy volunteers increased tenfold over 24 hours. But in people with Crohn's disease, blood flow increased only fourfold.

"There's nothing wrong with the cells. The messages to accumulate cells are missing," Segal explained.

"Zillions of bacteria are growing in the lining of the bowel and there's a very effective barrier, but sometimes it breaks down," he continued. "When this happens, bacteria get through to the wall of the bowel."

In normal people, the bacteria is gobbled up and cleared away. Not so in Crohn's, where a weakened immune response allows the bacteria to linger.

Restoring normal blood flow allows the necessary cell "workers" to clear away the problem. And because Viagra works by enhancing blood flow, the researchers decided to try it.

"We showed that Viagra restored the blood flow to almost normal levels, suggesting that it might be an effective therapy," Segal said.

Which doesn't mean Crohn's patients should go off their medication and start taking Viagra.

"Existing treatments are the best we've got," Segal warned. "We don't want people to go off them."

Thompson, however, said that the size of the study sample was too small to draw any real conclusions and also dismiss Viagra a non issue.

"It happened that the people with Crohn's, after the bacteria was injected, had a significantly diminished blood flow response, which Viagra was able to reverse. But the Viagra thing is really not at all important," he added.

More information

Learn more about Crohn's disease from the National Digestive Diseases Clearinghouse.

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