Interleukin 18: Tipping the Balance towards a T Helper Cell 1 Response

IL-18 was identified as a factor promoting IFN-γ production 1 and it was originally called IFN-γ–inducing factor (IGIF). Further study indicated IL-18 had a structure related to IL-1 2 and later it was found that the IL-18 receptor resembles that for IL-1 3,4. IL-18, like IL-1 and agents interacting with Toll receptors, signals via MyD88 which activates TNF receptor–associated factor and ultimately nuclear factor κB 5. Like IL-1, IL-18 is made as an inactive precursor that is cleaved by caspase-1 (interleukin-1–converting enzyme) to produce active cytokine 6. Many cell types have been reported to produce IL-18, including macrophages and dendritic cells 7; IL-18 mRNA or protein is also seen in Kupffer cells 8, astrocytes and microglia 9, intestinal and airway epithelial cells 10, and in kerotinocytes 11 and osteoblasts 12...