Interleukin-18 (IL-18) belongs to the IL-1 superfamily and is constitutively produced by macrophages, dendritic cells (DCs) and other cells. IL-18 binds to the receptor of IL-18 (IL-18R) and initiate the recruitment and heterodimerization of the IL-18RAcP, leading to downstream activation of NF-kappaB. After stimulation with IL-18, multiple cytokines including IFN-gamma, IL-13, IL-4, IL-8, and GM-CSF and both Th1 and Th2 lymphokines could be produced by different cells. As an immunoregulaory cytokine, IL-18 can promote development of T helper 1 (Th1) cells, which maximizes the production of IFN by synergistically stimulating to mature Th1 effectors in combination with IL-12. On the contrary, it inhibits the production of the anti-inflammatory cytokine IL-10. In addition, IL-18 exhibits multiple proinflammatory functions, such as increases in cell adhesion molecules, nitric oxide synthesis, and chemokine production.
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