Crohn’s disease is a chronic inflammatory disorder of the bowel, where lesions and ulcers form on the bowel walls. Many causes have been suggested for the disease, including infection with tuberculosis, other bacteria or viruses thought to trigger an excessive inflammatory response.
In the University College London (UCL) study, researchers investigated whether the disease is instead caused by impaired innate immunity. They found a defective immune response in Crohn’s sufferers, based on a lack of white blood cells sent to destroy bacteria.
Normally, when the immune system identifies an infection or injury, it produces cytokines which summon the most common form of white blood cells – neutrophils – to the infection site. When the neutrophils encounter bacteria they engulf, kill and digest the bacteria. Pus then forms, made up of dead neutrophils and other cell debris.
The team measured cytokine production (interleukin-8 or IL-8) and neutrophil recruitment at injury sites in the bowel and skin of Crohn’s patients and a control group of healthy individuals and patients with other types of inflammation. In a separate experiment, the left and right forearms were injected with heat-killed E.coli to study blood flow and the immune response to bacteria.
In the skin and bowel, the scientists found that Crohn’s patients had abnormally low levels of neutrophils and IL-8 at trauma sites. In the infected arms, they found a much lower blood flow response in Crohn’s patients compared with control subjects, where increased blood flow would normally carry the neutrophils to the infected sites. The team used impotence drug Viagra (sildenafil) to artificially correct the blood flood response to normal levels.
The findings suggest that, in Crohn’s disease sufferers, a weak immune response is failing to or delaying the elimination of bacteria in the bowel because of an ineffective neutrophil response. Instead, macrophages (another form of white blood cell) are containing the bacteria in granuloma that accumulate in the intestines, resulting in secondary, chronic inflammation.
Stimulation of blood flow with drugs such as Viagra could help compensate for the lack of neutrophil activity by carrying more neutrophils to the infected areas, the researchers concluded.