Overexpression of Interleukin-1β Induces Gastric Inflammation and Cancer and Mobilizes Myeloid-Derived Suppressor Cells in Mice

Polymorphisms of interleukin-1 beta (IL-1 beta) are associated with an increased risk of solid malignancies. Here, we show that stomach-specific expression of human IL-1 beta in transgenic mice leads to spontaneous gastric inflammation and cancer that correlate with early recruitment of myeloid-derived suppressor cells (MDSCs) to the stomach. IL-1 beta activates MDSCs in vitro and in vivo through an IL-1Rl/NF-kappa B pathway. IL-1 beta transgenic mice deficient in T and B lymphocytes develop gastric dysplasia accompanied by a marked increase in MDSCs in the stomach. Antagonism of IL-1 receptor signaling inhibits the development of gastric preneoplasia and suppresses MDSC mobilization. These results demonstrate that pathologic elevation of a single proinflammatory cytokine may be sufficient to induce neoplasia and provide a direct link between IL-1 beta MDSCs, and carcinogenesis.