Interleukin-1β induced by Helicobacter pylori infection enhances mouse gastric carcinogenesis.

Abstract Interleukin-1β ( Il1b ) is considered to be involved in Helicobacter pylori ( HP )-induced human gastric carcinogenesis, while the role of its polymorphisms in gastric cancer susceptibility remains controversial. Here, we aimed to clarify the role of HP infection-induced IL1B in gastric inflammation and carcinogenesis using Il1b −/− ( Il1b -null) mice. In gastric mucosa of the Il1b +/+ (WT) mice, HP infection induced Il1b expression and severe inflammation. In contrast, in Il1b -null mice, recruitment of neutrophils and macrophages by HP infection was markedly suppressed. In a carcinogenicity test, the multiplicity of gastric tumors was significantly suppressed in the Il1b -null mice (58% of WT; P  HP infection induced NF-κB activation both in the inflammatory and epithelial cells in gastric mucosae, and the activation was attenuated in the Il1b-null mice. Accordingly, increased proliferation and decreased apoptosis of gastric epithelial cells induced by HP infection in the WT mice were attenuated in the Il1b -null mice. These results demonstrated that the IL1B physiologically induced by HP infection enhanced gastric carcinogenesis by affecting both inflammatory and epithelial cells.