From Immunogenic Mechanisms to Novel Therapeutic Approaches in Inflammatory Bowel Disease
Martin H. Holtmann and Markus F. Neurath
Crohn’s disease (CD) and ulcerative colitis (UC) are the two most common forms of chronic inflammatory bowel disease (IBD). The etiology of IBD is still unclear and should be considered as multi-factorial according to recent studies.1 Genetic factors seem to play a pathogenetic role as well as environmental, infectious and immulogical factors. Substantial progress, however, has been made in the understanding of the pathogenesis of IBD during the past years persuing the view, that IBD could result from disturbances of the intestinal barrier and a pathologic activation of the intestinal immune response towards luminal, bacterial antigens. This paradigm has led to the identification of key players of the intestinal immune system, which represent promising targets for novel therapeutic approaches. The objective of this chapter is to provide an overview over recent advances in the elucidation of the intestinal immune system in IBD and novel therapeutic approaches that have been derived from these results. Molecular biological techniques have revealed, that many of the established conventional antiinflammatory drugs such as salicylic acids, steroids or immunuosuppressants act at the same molecules that are the target for modern biologicals, i.e., the cytokine TNF or the transcription factor NFkB. This chapter, however, focusses on novel experimental approaches such as recombinant antiinflammatory cytokines, neutralizing antibodies or antisense oligonucleotides.