Interleukin-18 regulates both Th1 and Th2 responses.
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.
Department of Immunology and Medical Zoology, Institute for Advanced Medical Sciences, Hyogo College of Medicine, Nishinomiya, Hyogo 663-8501, Japan. nakaken@hyo-med.ac.jp
K
K
Nakanishi
T
T
Yoshimoto
H
H
Tsutsui
H
H
Okamura
D000818:Animals; D001327:Autoimmune Diseases / Q000276:immunology; D001402:B-Lymphocytes / Q000187:drug effects / Q000276:immunology; D002454:Cell Differentiation / Q000187:drug effects; D016207:Cytokines / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism; D005786:Gene Expression Regulation / Q000187:drug effects; D006801:Humans; D006967:Hypersensitivity / Q000276:immunology; D007239:Infections / Q000276:immunology; D007371:Interferon-gamma / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism; D018664:Interleukin-12 / Q000502:physiology; D020382:Interleukin-18 / Q000096:biosynthesis / Q000737:chemistry / Q000235:genetics / Q000494:pharmacology / Q000502:physiology*; D053727:Interleukin-18 Receptor alpha Subunit; D008264:Macrophages / Q000187:drug effects / Q000378:metabolism; D051379:Mice; D018448:Models, Immunological; D005810:Multigene Family; D009928:Organ Specificity; D011498:Protein Precursors / Q000378:metabolism; D018123:Receptors, Interleukin / Q000737:chemistry / Q000187:drug effects / Q000235:genetics / Q000502:physiology; D053724:Receptors, Interleukin-18; D015398:Signal Transduction; D018417:Th1 Cells / Q000187:drug effects / Q000276:immunology* / Q000378:metabolism; D018418:Th2 Cells / Q000187:drug effects / Q000276:immunology* / Q000378:metabolism
D016207:Cytokines; C508572:IL18R1 protein, human; C508573:Il18r1 protein, mouse; D020382:Interleukin-18; D053727:Interleukin-18 Receptor alpha Subunit; D011498:Protein Precursors; D018123:Receptors, Interleukin; D053724:Receptors, Interleukin-18; D018664:Interleukin-12; D007371:Interferon-gamma