Lay Summary

Proposal No.  IBD-0201R
Principal Investigator:  Dirk Föll, M.D.
Applicant Organization:  University Hospital of Münster (Germany)
Project Title: Functional characterization of GM-CSF induced monocyte subsets and analysis of their relevance in Crohn's disease
Period of Award:  September 1, 2007 - August 31, 2010

Monocytes are believed to play a central role in the IBD. Consistently, drugs that act on monocytes, e.g., infliximab, are found to be highly effective in IBD. In a recently published clinical trial, “granulocyte-macrophage colony stimulating factor (GM-CSF)” has been shown to be efficient in the treatment of Crohn’s disease (CD). GM-CSF acts as a growth factor for monocyte precursor cells but can also influence mature inflammatory cells including monocytes. However, it is still not clear how GM-CSF exerts its beneficial activities in CD. Since GM-CSF is a growth factor it can induce proliferation of inflammatory cells. However, this cannot explain the observed anti-inflammatory effect. It seems more likely that GM-CSF affects inflammatory cells like monocytes and induces anti-inflammatory functions.

In previous studies using modern molecular biology techniques, we found that glucocorticoids, hormones that have been used for the therapy of IBD for decades, induced an anti-inflammatory monocyte phenotype. We will now compare the GM-CSF-induced response of monocytes from healthy donors with monocytes obtained from patients with CD, either having active disease or inactive disease without medication. We will also investigate whether GM-CSF or the GM-CSF receptor differs between healthy intestinal tissue and CD tissue. In addition, we will analyze how GM-CSF influences the cross-talk between the many immune cells that are involved during CD.

The aim of this study is to identify how GM-CSF exerts its beneficial effect in CD. We will clarify the effect of GM-CSF on monocytes as central cells of the innate immune system. This will also help in better understanding the role of the innate immune system in IBD and thus may help to develop new treatments strategies with fewer side effects due to more specific molecular targets.