Immunotherapeutic approaches to inflammatory bowel diseases

For a long time corticosteroids, aminosalicylic acid preparations and antibiotics have represented the principal approaches in evidence-based drug therapy for chronic inflammatory bowel diseases (IBD), e.g., Crohn's disease (CD) and ulcerative colitis (UC), and are able to suppress disease activity in most cases. However, there are cases that do not respond to conventional drug therapy or remain dependent on high doses of steroids associated with severe side effects in the long run. It is generally accepted now that IBD has an immunological basis and results from a hyperresponsive state of the intestinal immune system. Although the primary etiological defect respectively immunogenic agent still remains to be identified, substantial progress has been made in our understanding to regulatory mechanisms of the intestinal immune system and their alterations in IBD at the molecular level. Due to the concurrent advent of biotechnological processes it has been possible to utilise these insights for the development of novel immunomodulatory therapeutic strategies ranging from recombinant cytokines and blocking antibodies to oligonucleotide antisense strategies and gene therapeutic approaches. This review will present the current status of the development of these novel immunomodulatory therapeutic strategies in IBD and the status of their use in clinical practice. For a better understanding, it will be necessary to address the recent advances in the elucidation of pathogenetic mechanisms of IBD from studies in human specimen and experimental colitis models that have provided the basis for these novel therapeutic approaches.