Interleukin-18 (IL-18) is a multifunctional cytokine belonging to the IL-1 superfamily. It plays a crucial role in both innate and acquired immunity, regulating interferon-gamma production in Th1 responses by synergizing with IL-12. IL-18 enhances innate immune responses by inducing the production of other cytokines like GM-CSF, TNF-α, and IL-1β.
Initially identified as interferon-gamma inducing factor (IGIF), IL-18, unlike IL-1β, is abundantly present in normal cells, with inflammation having minimal impact on its production. IL-18 precursor is expressed in various cell types including macrophages, dendritic cells, keratinocytes, chondrocytes, synovial fibroblasts, and osteoblasts.
Further research has revealed multiple secretion mechanisms for IL-18. Apart from being secreted as an inactive protein and processed into an active form by Caspase-1, PR3-induced IL-18 secretion is Caspase-1 independent. Fas signaling activates Caspase-8 in macrophages and dendritic cells, leading to IL-18 secretion. Additionally, under VEGF-D stimulation, GC cells secrete IL-18 in a manner associated with ADAM33.
