Anti-IL-6 treatment for inflammatory bowel diseases: next cytokine, next target

Inflammatory bowel diseases (IBD) are chronic, relapsing, and destructive inflammatory disorders of the gastrointestinal tract. Both Crohn's disease (CD) and ulcerative colitis (UC) seem to arise from an impaired dialog between the environment and gut microbiota in genetically susceptible hosts, leading to an inappropriate immune activation and resulting in the over-production of pro-inflammatory cytokines. IL-6 is a key modulator of inflammatory response. It is a phylogenetically important cytokine with relevance in IBD, as well as in other chronic inflammatory diseases and cancer. Influencing the production of this cytokine can change the balance of effector CD4+ T cell subsets and induce B cell antibody production. Moreover, given IL-6 is mostly produced from innate immune cells such as macrophages, neutrophils and mast cells, it is a strategic bridge between the innate and the adaptive system. Interestingly, IL-6 induced signaling can be primarily seen in a relatively small number of IL-6 responsive cells whereas in a chronic phase of inflammation it is able to activate almost all cells of the body through a process known as trans-signaling. In this review, we discuss the role of IL-6 in chronic inflammation, with particular emphasis on its role in CD and UC, and we explore the potential to develop anti-IL-6 agents for IBD treatment.