Mechanistic roles of interleukin‑18 in colonic immunity across infection, inflammatory bowel disease, and colorectal cancer (Review)

The colon, functioning as a central organ for digestion, absorption, and immune defense in the human body, depends on intricate interactions among the epithelial barrier, immune cells, and gut microbiota to sustain mucosal homeostasis. Dysregulation within cytokine networks constitutes a key pathogenic driver of colonic disorders, including inflammation, infection, and tumorigenesis. Interleukin (IL)‑18, a pivotal cytokine in colonic immune modulation, exhibits dual roles in maintaining homeostasis and mediating pathology: IL‑18 orchestrates immune responses through both inflammasome‑dependent and ‑independent mechanisms, exerting bidirectional influences on colonic pathogen eradication and inflammatory exacerbation. The coordinated actions of IL‑18 and IL‑22, mediated via epithelium‑specific receptor signaling, primarily govern colonic barrier restoration and antimicrobial defense, undergoing functional transitions throughout disease progression. The present review systematically elucidates the molecular characteristics of IL‑18 and its mechanistic functions in colonic pathogen defense and disorders such as inflammatory bowel disease and colorectal cancer, following the logical framework of molecular mechanisms, physiological roles, pathological regulation, and interactive networks. The synergistic and antagonistic interactions among IL‑18 and IL‑22 are analyzed, and their clinical translational potential is explored, providing a theoretical basis for precision intervention in colonic pathologies. Based on clinical and mechanistic studies, this review systematically integrates existing experimental evidence to provide a theoretical framework for understanding the complex roles of IL‑18 in colonic immunity. Although targeted intervention of IL‑18 holds promise in animal models, its clinical translation warrants further validation through human studies, given its context‑dependent functions and potential risks.