Disruption of inflammatory signals by cytokine-targeted therapies for inflammatory bowel diseases

Gut inflammation occurring in patients with inflammatory bowel diseases (IBD) is associated with an excessive immune response that is directed against constituents of the normal bacterial flora and results in the production of large amounts of inflammatory cytokines. Anti-cytokine compounds, such as the neutralizing TNF antibodies, have been employed with clinical success in patients with IBD. However, nearly half of IBD patients are refractory to such treatments, response can wane with time, and anti-TNF treatment can associate with severe side effects and/or development/exacerbation of extra-intestinal immune-mediated pathologies. These observations, and the demonstration that, in IBD, the pathological process is also characterized by defects in the production and/or activity of counter-regulatory cytokines, have boosted further studies aimed at delineating novel strategies to combat the IBD-associated tissue-damaging immune response.