Community Research and Development Information Service - CORDIS

FP7

RIFEK Result In Brief

Project ID: 294253
Funded under: FP7-PEOPLE
Country: Germany

Interleukin-10 and inflammatory bowel disease

Over 2 million people in Europe suffer from inflammatory bowel disease (IBD). Finding treatments requires an in depth understanding of the underlying mechanism.
Interleukin-10 and inflammatory bowel disease
IBDs such as Crohn's disease and ulcerative colitis are chronic inflammatory conditions that primarily affect the gut but can also have systemic manifestations. The prevailing hypothesis is that IBD is caused by excessive immune responses against harmless bacteria in the intestine. Under physiological conditions, interleukin-10 (IL-10) acts through a negative feedback loop via its receptor (IL-10R) to regulate and avoid excessive pro-inflammatory responses.

Patients with mutations in IL-10 or IL-10R genes present with severe inflammation of the gut during the first months of life. These deficiencies are life threatening and can only be cured by bone marrow transplantation.

Scientists on the EU-funded RIFEK (Revisiting immunomodulatory functions of IL10 by examining human knock-outs) project established a European network of specialists in the field and collected samples from over 100 children with severe inflammation of the gut. The ultimate goal was to delineate the mechanism underlying the pathology of IL-10/IL-10R patients. Genetic analysis revealed that several of these children had defective IL-10R and underwent bone marrow transplantation.

IL-10R deficient patients showed increased numbers of IL-17-producing T lymphocytes (Th17 cells) and IL-17/IFN-gamma producing T lymphocytes known to be associated with IBD. These potentially tissue-damaging T lymphocytes were also increased in IBD patients with normal IL-10 function, indicating a potential role of this cytokine in the development of IBD. IL-10R deficient patients also had increased levels of pro-inflammatory cytokines.

Taken together, the results of the RIFEK project demonstrated the role of IL-10 signalling in gut inflammation and potentially in IBD. Genetic screening can help deficient patients receive life-saving bone marrow transplantation. It remains to be determined whether a similar approach or IL-10 administration could work as a treatment in IBD patients.

Related information

Keywords

Interleukin-10, inflammatory bowel disease, IL-10 receptor, bone marrow transplantation, Th17 cells
Record Number: 190515 / Last updated on: 2016-11-10
Domain: Biology, Medicine