Fresh theory on cause of Crohn's Disease
Friday, 24 February 2006, 00:11 GMT
A weakened immune system - not an over-active one as had been suspected - may cause the intestinal disorder Crohn's disease, research suggests.
However, work by University College London (UCL) suggests Crohn's is more likely to be due to a weakened immune system failing to destroy bacteria.
The Lancet study also suggests the anti-impotence drug Viagra may help to treat the disorder.
Viagra was found to correct low blood flow among Crohn's sufferers.
Crohn's disease is a chronic inflammatory disorder that causes ulcerations in the small and large intestines.
The UCL team compared the immune system response of Crohn's patients and healthy individuals to minor injuries, such as skin abrasions.
They found the Crohn's patients produced much lower numbers of infection-fighting white blood cells called neutrophils, and lower quantities of chemicals involved in the inflammatory process.
Blood cells taken from Crohn's patients also turned out to be abnormal when cultured in the laboratory.
E. coli infection
The UCL team also tested Crohn's patients' response to bacteria by injecting a harmless form of E. coli under their skin.
This resulted in a huge increase in blood flow to the inflamed area in healthy volunteers - but a much smaller increase in the Crohn's patients.
The researchers found this abnormally low blood flow could be corrected by treatment with Viagra.
The researchers believe that, because Crohn's patients have weakened immune systems, they are unable to destroy bacteria that penetrate the intestinal wall.
Thus the bacteria are left to build up in the tissue, stimulating the secretion of inflammatory chemicals that trigger the symptoms of Crohn's.
Dr Alistair Forbes, medical director of the gut disorder organisation Core, told the BBC News website the work was "very exciting" and consistent with other pieces of work which suggested Crohn's was linked to a weak immune response.
Dr Forbes said Crohn's patients had been reported to benefit from a treatment usually given to cancer patients to stimulate the production of white blood cells.
If Crohn's were an auto-immune disease then one would expect this treatment to make patients worse, rather than better.
In addition, a mutation of a gene linked to Crohn's was thought to weaken, rather than intensify the immune response.
He said: "The cause of Crohn's remains unknown, and although there are genetic factors, it is quite clear they don't explain the whole thing.
"Crohn's is clearly related to the bacterial flora in the gut, but how is not clear at all.
"There are several pieces of information that suggest Crohn's is linked to an abnormality of the immune response, rather than an excessive one in the first instance."