The primary question in this research project is how the nervous system influences the immune system. The focus lies on the inflammatory diseases in the gastrointestinal tract like Crohn's disease and ulcerative colitis, and on inflammation arising in the intestinal wall after abdominal surgery. The research principles are also applicable to other inflammatory diseases like rheumatoid arthritis. The ultimate goal is to find medicinal products that imitate the beneficial effect of substances from the nervous system.

The nervous system consists of two components: the adrenergic (activating) and the cholinergic (sedating) systems. In vitro and in animal models, studies have been done of how substances from these two systems, noradrenaline and acetylcholine, respectively, affect the immune system and thus influence the extent of inflammation. Earlier research had shown that inflammation could be suppressed by electrical stimulation of the vagal nerve (cranial nerve), and thus of the cholinergic system. Within this research project this mechanism will be examined in detail, searching for a similar action of the adrenergic system. Finally, the researchers will explore the role of the nervous system in the gastrointestinal tract itself.

Fast facts
Full project title: Neuromodulation of innate immune responses
Project theme: inflammatory diseases
Start date: January 2007
End date: January 2012
Goal: influencing the immune system via the nervous system
Name of PI and organization: Guy Boeckxstaens, AMC, University of Amsterdam
Number of investigators active in this project: 14 FTE
Partners: Groningen University Medical Centre, Academic Medical Centre of the University of Amsterdam, GlaxoSmithKline

Background

Inflammation of the gastrointestinal tract is common. For example, patients after major abdominal surgery can develop an inflammation of the intestinal wall, a postoperative ileus, which prevents proper functioning of the gastrointestinal tract. The inflammation is caused by cells from the immune system. The inflammation often extends the patient's hospital stay. 

In addition, there are several forms of chronic gastrointestinal tract inflammation. The two most prevalent disorders are Crohn's disease and ulcerative colitis. In both these diseases, part of the gastrointestinal tract is inflamed. Crohn's disease can occur throughout the entire gastrointestinal tract, while ulcerative colitis is restricted to the large intestine. Diarrhea, stomach ache and fever are the main symptoms; many patients also suffer from inflammation elsewhere in the body and osteoporosis. 

Currently, there are no medicinal products available to cure chronic gastrointestinal tract inflammation. Therefore, the treatment consists of anti-inflammatory agents. Surgery may also be necessary. In the Netherlands there are about 55,000 people with a chronic gastrointestinal tract inflammation.

PhD theses from this project

Susanne Snoek (project T1-215)
Neuro-immunity in intestinal disease

Esmerij van der Zanden (project T1-215)
The vagus nerve as a modulator of intestinal inflammation

 

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Hugo Hurts
Director/Secretary of the Medicines Evaluation Board

Hugo Hurts
Director/Secretary of the Medicines Evaluation Board

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