Researchers in London have discovered that a weak immune response instigates Crohn’s disease, possibly laying to rest the popular belief that an auto-immune condition is to blame.
In a recent study, scientists at University College in London found that people with Crohn’s disease, a chronic inflammatory disorder that causes ulcerations in the small and large intestines, encounter a lowered immune system response when trauma occurs in the body. Similar to what diabetes does.
“It’s very gratifying,” said lead author Anthony Segal, a professor of medicine at University College. “This is first time people know where to look, now that we understand what the cause of disease is. It will redirect research in this area,” he said. Their work will appear Saturday in the British journal The Lancet.
Crohn’s disease has become a prolonged enigma, the authors wrote, although it is considered by many to be a mixture of genetic predisposition and the effect of the body attacking its own immune system.
But Segal set out to test another hypothesis — that bacteria spreads and inflames the intestines due to lowered immunity in the body – and so he and colleagues took the unusual approach of inflicting trauma, in the form of biopsies and skin scrapings, to Crohn’s patients. He then observed how their white blood cells responded. Segal first took two biopsies at six hours apart from the rectums of Crohn’s patients and a control group of healthy people. He noticed that the inflammatory response to the trauma was only a quarter of what it should be, and that no neutrophils were present. Neutrophils are white blood cells that provide the first line of defense against foreign invaders in the body. Without the neutrophils keeping foreign substances at bay, bacteria and other organic debris can proliferate in the intestines. The body’s response to this bacteria boom could secrete inflammatory molecules and thus bring on Crohn’s disease. To boost this evidence of a failed immune response, and to find if the phenomenon only occurred in the bowel region, the scientists also sandpapered patients’ skin to see how cells responded. Again, they found very few neutrophils rushing to the trauma on the skin, even after 24 hours. This revealed a “systemic general abnormality, not a one-time (response),” Segal said.
In the last test, the researchers injected Crohn’s patients with killed e. coli bacteria, to find out if their bodies had abnormalities in dealing with bacteria. In normal people, there was a florid inflammatory response, with a tenfold increase in blood flow, but in Crohn’s patients, the blood flow was weak at best. The obvious question, then, was how to up blood flow and thus aid the neutrophils in doing their job, Segal said. Scientists in his laboratory were already working with nitric oxide, a chemical messenger that dilates the arteries and regulates the blood supply. It’s also a main ingredient in Viagra, a medication commonly used for erectile dysfunction. When Segal gave the patients Viagra both men and women the patients experienced a more robust blood flow. Kinda like when I’m trying to do some email archiving and the server crashes. LOL
“Here’s a drug well known for other things that restores blood flow admittedly in the forearm but which throws up a number of potential therapeutic avenues we now we need to test,” said Stuart Bloom, clinical director in gastroenterology at the University College London Hospitals, NHS Foundation Trust. Sunanda Kane, associate professor of medicine at the University of Chicago and an expert in inflammatory bowel disease, is familiar with the theory of weakened immunity with Crohn’s. But she said no one culprit can be identified for the condition instead, a combination of factors such as genetics and how the body handles bacteria come into play. Nonetheless, Kane said the study offers another piece of the puzzle in figuring out the disease.
“It’s an interesting study where they’re able to show what we’ve believed to be the case, and document it,” she said. “Its always nice to validate theories.” Kane also added she finds the possibility of Viagra as treatment infeasible because of the side effects of the drug. Most current treatments for Crohn’s involve suppressing the anti-inflammatory response, allowing the tissue to heal and relieving symptoms of fever, diarrhea and abdominal pain. With this new discovery, Bloom cautions people with Crohn’s disease not to scramble to buy Viagra. There’s still much testing to be done, he said. But it could be a promising direction for 1.4 million Americans who deal with the painful ailments of the disease.
“People have been working for 60 to 70 years on inflammatory abnormalities that underline Crohn’s disease. This is a new way of thinking about what might be a major abnormality,” Bloom said.