Targeting tumor necrosis factor-alpha in inflammatory bowel disease: why, how, and when?

A large proportion of patients with inflammatory bowel disease require more effective therapy, especially for the prevention of disease relapse. Recent therapeutic advances have focused on biologicals (monoclonal antibodies, therapeutic peptides, antisense oligonucleotides) that aim to neutralize specific proinflammatory proteins. This has proved successful for the anti-TNF-alpha antibody infliximab in patients with Crohn disease, but recent studies failed to demonstrate the efficacy of different anti-TNF-alpha strategies. Therefore, it seems essential to fully comprehend the molecular mechanisms of such compounds. An exciting development has been the association between drug efficacy and the induction of apoptosis in apoptosis-resistant lamina propria T cells in Crohn disease. Furthermore, TNF-alpha can also be targeted by "small molecules" to circumvent certain disadvantages of biologicals such as the nonoral route of administration, the potential immunogenicity, and the high costs of treatment. Several of these developments will certainly be relevant for designing future anti-TNF-alpha based strategies.