The interleukin-1 (IL-1), IL-18, and IL-33 families of cytokines share similar mechanisms of origin, receptor structure, and signal transduction pathways. These cytokines are synthesized as precursor molecules and cleaved by caspase-1 to become biologically active. The NALP-3 inflammasome is crucial for generating active caspase-1. The IL-1 family includes IL-1α, IL-1β, IL-1Ra, and two receptors, IL-1R1 and IL-1R2. The IL-18 family consists of IL-18 and IL-18BP, with the IL-18 receptor similar to the IL-1 receptor complex. IL-33 binds to the orphan receptor T1/ST2 and stimulates T-helper 2 responses and mast cells. Excess production of IL-1 has been implicated in various human diseases, and the balance between IL-1 and IL-1Ra is important for preventing disease. IL-18 provides a link between innate and adaptive immune responses, and its production is regulated by microbial components and caspase-1 activation. IL-18BP acts as a natural inhibitor by binding to mature IL-18. IL-18 is involved in the clearance of intracellular pathogens and induces IFN-γ production by Th1 cells. It also stimulates Th2 and Th17 responses and enhances the activity of NK cells and CD8+ T cells. IL-18 is elevated in multiple sclerosis, arthritis, inflammatory bowel diseases, and psoriasis, and its inhibition can reduce disease severity. In atherosclerosis, IL-18 has opposing effects, promoting plaque destabilization but also contributing to metabolic syndrome.The interleukin-1 (IL-1), IL-18, and IL-33 families of cytokines share similar mechanisms of origin, receptor structure, and signal transduction pathways. These cytokines are synthesized as precursor molecules and cleaved by caspase-1 to become biologically active. The NALP-3 inflammasome is crucial for generating active caspase-1. The IL-1 family includes IL-1α, IL-1β, IL-1Ra, and two receptors, IL-1R1 and IL-1R2. The IL-18 family consists of IL-18 and IL-18BP, with the IL-18 receptor similar to the IL-1 receptor complex. IL-33 binds to the orphan receptor T1/ST2 and stimulates T-helper 2 responses and mast cells. Excess production of IL-1 has been implicated in various human diseases, and the balance between IL-1 and IL-1Ra is important for preventing disease. IL-18 provides a link between innate and adaptive immune responses, and its production is regulated by microbial components and caspase-1 activation. IL-18BP acts as a natural inhibitor by binding to mature IL-18. IL-18 is involved in the clearance of intracellular pathogens and induces IFN-γ production by Th1 cells. It also stimulates Th2 and Th17 responses and enhances the activity of NK cells and CD8+ T cells. IL-18 is elevated in multiple sclerosis, arthritis, inflammatory bowel diseases, and psoriasis, and its inhibition can reduce disease severity. In atherosclerosis, IL-18 has opposing effects, promoting plaque destabilization but also contributing to metabolic syndrome.