IL-18 is a pro-inflammatory cytokine with dual roles in immunity and disease pathogenesis. Functionally, IL-18 promotes epithelial barrier repair and polarized Th1 cell and natural killer (NK) cell responses 1. Upon binding to its receptors IL18R1 and IL18RAP, IL-18 forms a signaling ternary complex that activates NF-κB, triggering synthesis of inflammatory mediators 234. The cytokine synergizes with IL-12 to induce interferon-gamma synthesis from Th1 and NK cells. Mechanistically, mature IL-18 is released extracellularly through gasdermin-D pores following pyroptosis 5, while alternative processing generates bioactive fragments with distinct functions, including a 15-kDa form that enhances anti-tumor NK cell activity 6. Clinically, IL-18 dysregulation associates with multiple pathologies: elevated serum and tissue IL-18 correlates with atopic dermatitis severity and type 2 immune responses 7, while aberrant IL-18 signaling promotes tumor immune evasion and progression through CXCL1/CXCL5-mediated myeloid recruitment 8. Conversely, IL-18-secreting CAR T cells demonstrate enhanced anti-tumor efficacy 9. IL-18 blockade shows therapeutic promise in inflammatory diseases including obesity-associated inflammation 10 and gallbladder cancer 11. These findings establish IL-18 as a multifaceted immunomodulator with significant therapeutic potential.