IL-18 (Interleukin-18) is secreted by macrophages, dendritic cells, and epithelial cells. Circulating mature IL-18 is sequestered by soluble IL-18 binding proteins (IL-18 BP) that inhibit IL-18 bioactivity. IL-18 signals through a receptor complex that contains IL-18 R alpha IL-18 R beta. It synergizes with other cytokines to activate NK, Th1, and Th17 cells and to increase the production of IFN-gamma. It can also promote Th2 cytokine release which reduces the effectiveness of antiviral responses. Increased levels of active IL-18 contribute to the severity of autoimmunity and hypertension, while deficiency of IL-18 results in symptoms of metabolic syndrome. In cancer, IL-18 stimulates Th1 and NK cells to target tumor cells, but it can also promote angiogenesis, metastasis, and tumor cell immune evasion.