Abstract
Although interleukin-18 is structurally homologous to IL-1 and its receptor belongs to the IL-1R/Toll-like receptor (TLR) superfamily, its function is quite different from that of IL-1. IL-18 is produced not only by types of immune cells but also by non-immune cells. In collaboration with IL-12, IL-18 stimulates Th1-mediated immune responses, which play a critical role in the host defense against infection with intracellular microbes through the induction of IFN-gamma. However, the overproduction of IL-12 and IL-18 induces severe inflammatory disorders, suggesting that IL-18 is a potent proinflammatory cytokine that has pathophysiological roles in several inflammatory conditions. IL-18 mRNA is expressed in a wide range of cells including Kupffer cells, macrophages, T cells, B cells, dendritic cells, osteoblasts, keratinocytes, astrocytes, and microglia. Thus, the pathophysiological role of IL-18 has been extensively tested in the organs that contain these cells. Somewhat surprisingly, IL-18 alone can stimulate Th2 cytokine production as well as allergic inflammation. Therefore, the functions of IL-18 in vivo are very heterogeneous and complicated. In principle, IL-18 enhances the IL-12-driven Th1 immune responses, but it can also stimulate Th2 immune responses in the absence of IL-12.
Publication types
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Research Support, Non-U.S. Gov't
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Review
MeSH terms
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Animals
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Autoimmune Diseases / immunology
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B-Lymphocytes / drug effects
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B-Lymphocytes / immunology
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Cell Differentiation / drug effects
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Cytokines / biosynthesis
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Cytokines / genetics
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Cytokines / metabolism
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Gene Expression Regulation / drug effects
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Humans
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Hypersensitivity / immunology
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Infections / immunology
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Interferon-gamma / biosynthesis
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Interferon-gamma / genetics
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Interferon-gamma / metabolism
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Interleukin-12 / physiology
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Interleukin-18 / biosynthesis
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Interleukin-18 / chemistry
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Interleukin-18 / genetics
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Interleukin-18 / pharmacology
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Interleukin-18 / physiology*
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Interleukin-18 Receptor alpha Subunit
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Macrophages / drug effects
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Macrophages / metabolism
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Mice
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Models, Immunological
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Multigene Family
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Organ Specificity
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Protein Precursors / metabolism
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Receptors, Interleukin / chemistry
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Receptors, Interleukin / drug effects
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Receptors, Interleukin / genetics
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Receptors, Interleukin / physiology
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Receptors, Interleukin-18
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Signal Transduction
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Th1 Cells / drug effects
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Th1 Cells / immunology*
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Th1 Cells / metabolism
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Th2 Cells / drug effects
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Th2 Cells / immunology*
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Th2 Cells / metabolism
Substances
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Cytokines
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IL18R1 protein, human
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Il18r1 protein, mouse
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Interleukin-18
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Interleukin-18 Receptor alpha Subunit
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Protein Precursors
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Receptors, Interleukin
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Receptors, Interleukin-18
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Interleukin-12
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Interferon-gamma