4th Annual BMRP Investigator Meeting - Abstract
Heat Shock Proteins as Therapeutic Agents for Inflammatory Bowel Disease
Ruurd van der Zee1,a, Miloslav Kverka2 , Femke Hauet-Broere1, Raymond H.H. Pieters3, Marianne W.H.C. Bol-Schoenmakers3, Helena Tlaskalová-Hogenová2 and Willem van Eden1,b
1Department of Infectious Diseases and Immunology, Utrecht University (Utrecht, The Netherlands); 2Department of Immunology and Gnotobiology, Institute of Microbiology, Academy of Sciences of the Czech Republic, 1st Faculty of Medicine, Charles University (Prague, Czech Republic); 3Department of Immunotoxicology, Institute for Risk Assessment Sciences, Utrecht University (Utrecht, The Netherlands).
Heat shock proteins (HSP) and derived peptides can be used as therapeutic agents to prevent or arrest the inflammatory damage in both experimental arthritis and in experimental diabetes. One of the mechanisms involved can be the expansion of regulatory, microbial (commensal) HSP reactive T cells that are cross-reactive with homologous self-HSP over-expressed in inflamed tissue. This cross-reactivity leads to regulatory cytokine production at the site of inflammation, such as IL-10, a cytokine known to have protective qualities in IBD. In our studies, we investigate whether administration of HSP can have similar protective effects in experimental models of IBD, which HSP are most effective and to find the most optimal route of administration.
In our studies in the model of DSS-induced colitis in BALB/c mice, we now find that oral administration of microgram amounts of mycobacterial HSP60 is reproducibly disease suppressive (with respect to weight losses, colon length, overall clinical state and histological grade) when given prior to disease induction. Minor effects were observed with an HSP60 peptide(containing a CD4+ T cell epitope) given orally. Studies in the model of TNBS-induced colitis are in progress.
aCo-investigator and Presenter; bPrincipal Investigator