Interleukin 18

By S. Swain. Journal of Experimental Medicine, 2001

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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 34. 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. What induces IL-18 has not been extensively studied, but IL-18 is found after bacterial 13 and viral 14 infection and, by inference, in many other infectious diseases. IL-18 production from many cells is constitutive or prolonged after induction 15. An important, but not well-explored, role for IL-18 can also be inferred from the fact that poxviruses make a homologue of IL-18–binding protein, a natural suppressor of IL-18 16 and also an inhibitor of interleukin-1–converting enzyme 17.

Subfields: Hematology, Immunology, Molecular Biology

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