Targets for new immunomodulation strategies in inflammatory bowel disease

Crohn's disease (CD) and ulcerative colitis (UC), the major forms of inflammatory bowel diseases (IBD) in human beings, are characterized by damage to the intestinal epithelium and deeper layers, which is caused by an excessive immune response directed against normal constituents of the gut microflora. In both IBD, the diseased tissue is heavily infiltrated with several subsets of leukocytes that produce huge amounts of inflammatory cytokines whose profiles varies not only between CD and UC but also during the evolution of the same disease. These recent discoveries together with the demonstration that the inhibition of some soluble cytokines is not beneficial in IBD have contributed to delineate new scenarios by which tissue damage is induced and perpetuated. We here review some of the major immunological defects documented in IBD and discuss why compounds inhibiting soluble cytokines were not beneficial in patients and how we can optimize therapeutic strategies with biologics.