Role for IL-1 in mucosal barrier injury. The development of mucosal barrier injury (mucositis) is traditionally described as consisting of 5 stages. (1) DNA and non-DNA damage is initiated by chemotherapy or radiotherapy, and ROS are generated. (2) Transduction pathways are activated, stimulating transcription factors such as NF-κB. Many genes are upregulated, resulting in the production of proinflammatory cytokines (eg, TNFα, IL-1β, and IL-6), after which epithelial cell death and injury occur. (3) Primary damage is amplified by a positive-feedback loop of proinflammatory cytokines. (4) Ulceration occurs, and increased permeability with impaired tight junctions results in bacterial translocation. (5) Repair and healing. N indicates normal mucosa in the small intestine.