Dupilumab to target interleukin 4 for inflammatory bowel disease? Hypothesis based on a translational message

Dupilumab is a human monoclonal antibody that has recently been approved for the treatment of mild-to-severe atopic dermatitis. Dupilumab inhibits the interleukin (IL)-4/IL-13 signalling by binding specific subunits of the receptors. IL-4 is involved in the regulation of both innate and adaptive intestinal immune system, thus its possible role in the pathogenesis of inflammatory bowel disease (IBD) has been investigated. Several polymorphisms of IL-4 have been found in patients with IBD. Furthermore, the crucial role of IL-4 has been demonstrated in Th2-driven models of colitis as well as in Th1-related models of this disease. Finally, many studies have shown the increased production of IL-4 in two models of experimental colitis: the dextran sulphate sodium - related colitis and the oxazolone-related colitis. In the latter, a dual antagonist of IL-4/IL-13 has proved to ameliorate the course of the disease. In conclusion, IL-4 antagonists might play a role in the treatment of IBD, especially in ulcerative colitis, which shows a classic pattern of Th2-related disease.