Final Progress Report

Proposal No. IBD-0159
Principal Investigator:  Willem van Eden, M.D., Ph.D.
Applicant Organization:  Utrecht University (The Netherlands)
Project Title:  Heat shock proteins as therapeutic agents for inflammatory bowel disease
Period of Award:  September 1, 2005 – February 29, 2008

Lay Summary of Progress Report

Inflammatory bowel disease (IBD) is a group of chronic inflammatory diseases.  All inflammatory processes do lead to the production of cellular stress proteins (also called heat shock proteins or HSPs).  The immune system has the capacity to respond to the (upregulated) presence of HSP in tissues and this response has a regulatory and anti-inflammatory nature.  By the exogenous administration of HSPs, this response and, in particular, its regulatory anti-inflammatory nature, can be further activated and enhanced.  In several chronic inflammatory diseases such as arthritis and type 1 diabetes, this aspect of stress proteins or HSPs has been analyzed in models and the findings have been translated into experimental interventions in humans with so far very promising results.  

The aim of this project was to investigate whether or not this approach can be used for the development of a new treatment for IBD.  Given the fact that HSPs are a normal constituent of bacteria and other cellular micro-organisms, immune exposure to such antigens is very physiological.  Therefore, this approach, when effective, was expected to be without serious side-effects.

In a chemically induced model of colitis in mice it was found that the oral administration of HSPs suppressed several disease indicators of disease both when given before or during disease. To verify the general applicability the approach was tested in other models of colitis. In one other chemically induced model the administration of HSPs was not found successful to suppress disease.

In a third model in which it was tested whether HSPs could be used to vaccinate against colitis the results so far were not conclusive.  Therefore, our studies to evaluate the usefulness of HSPs for treatment of IBD have not yet finished and will be continued.