Novel strategies to attenuate immune activation in Crohn's disease.

Our understanding of the pathogenic mechanisms that underlie the chronic intestinal inflammation characteristic of Crohn's disease (CD) has advanced greatly in recent years. We now realize that effective treatment will not be achieved through non-specific generalized immunosuppression, but rather with the development of well-designed therapies that target specific immunological pathways. The success of infliximab has driven exploration into the blockade of additional pro-inflammatory cytokines, such as interleukin-12 and interferon-gamma. Novel strategies have also emerged that target other components of the inflammatory cascade, such as the migration of leukocytes to the intestine. The identification of mutations in the nod2/card15 gene that are associated with a predisposition for the development of CD has focused attention on the role of the innate immune system in CD. This has allowed a fundamentally different approach to the development of therapies for CD aimed at intensifying innate immune responses. In parallel with the development of several 'biological' agents, alternative therapeutic options have also shown promising results. The use of probiotic bacteria as both therapeutic agents and delivery vehicles for other molecules is a rapidly developing field. As the role of regulatory T cells in the pathogenesis of CD is revealed, the potential of immunotherapy is being opened up. With so many therapeutic options in sight and the ongoing elucidation of the pathogenesis of CD, it will become steadily more possible to tailor treatment to the clinicopathological and immunogenetic profile of the individual patient.