Master regulator of intestinal disease: IL-6 in chronic inflammation and cancer development

• IL-6 is a pleiotropic cytokine involved in the regulation of innate and adaptive immunity.
• IL-6 regulates chronic intestinal inflammation by regulating the balance between pro- and anti-inflammatory T cells.
• Trans signaling of IL-6 promotes tumor growth in CRC through intracellular STAT3 activation.
• Various therapeutics targeting IL-6 signaling has been developed for the treatment of human disease during recent years.
• Initial clinical studies show promising results for IL-6 inhibition in human inflammatory diseases and cancer.

IL-6 signaling is of central importance for the maintenance of chronic intestinal inflammation in inflammatory bowel diseases (IBD) such as Crohn's disease and ulcerative colitis. IL-6 regulates T cell differentiation, activation and resistance against apoptosis and thereby controls the balance between pro-inflammatory T cell subsets such as Th1 or Th17 cells and immunosuppressive regulatory T cells. Furthermore, IL-6 has been implicated in the pathogenesis of colorectal cancer (CRC). In fact, IL-6 directly promotes tumor cell proliferation and survival through STAT3 activation. Due to its role in both types of diseases, IL-6 has been proposed as a missing link between inflammation and tumor development. During recent years, several therapeutics targeting IL-6 dependent pathways have been developed. Although clinical data about anti-IL-6 treatment in intestinal diseases are currently scarce, targeting this pathway might be a promising strategy in IBD and CRC.