Gut reaction: the case against IL-23

The prime suspect behind inflammatory bowel disease (IBD) has been wrongly accused. Work by Hue et al. (page 2473) and Kullberg et al. (page 2485) reveals that the cytokine IL-12 was merely a cover for the real IBD culprit, IL-23. IL-23 promotes inflammation by corrupting not only adaptive immunity, as previously thought, but also the innate immune system.

IL-12, an activator of adaptive immunity via the induction of Th1 cells, is composed of two subunits, p35 and p40. In mouse models of intestinal inflammation, antibodies against p40 prevent the chronic inflammation that occurs in IBD in response to intestinal bacteria. Thus, IL-12 was considered responsible for driving IBD.

Case closed? Not quite. In 2000, it was discovered that p40 can also dimerize with p19 to form IL-23. Thus, all studies using antibodies against p40, including...