Interleukin-18 is a unique cytokine that stimulates both Th1 and Th2 responses depending on its cytokine milieu.
IL-18 is a potent proinflammatory cytokine able to induce IFNgamma, GM-CSF, TNFalpha and IL-1 in immunocompetent cells, to activate killing by lymphocytes, and to up-regulate the expression of certain chemokine receptors. IL-18 is also essential to host defences against severe infections. In particular, the clearance of intracellular bacteria, fungi and protozoa requires the induction of host-derived IFNgamma, which evokes effector molecules such as nitric oxide. Also, IL-18 plays a part in the clearance of viruses, partly by the induction of cytotoxic T cells, and the expulsion of viruses is impaired in IL-18-deficient mice. IL-18 also enhances tumour rejection by its potent capacity to augment the cytotoxic activity of NK and T cells in vivo. In contrast, recent studies also demonstrate a convincing role for IL-18 in atopic responses, including atopic asthma. IL-18 induces naive T cells to develop into Th2 cells. Moreover, IL-18 also induces IL-13 and/or IL-4 production by NK cells, mast cells and basophils. Therefore, IL-18 should be seen as a unique cytokine that enhances innate immunity and both Th1- and Th2-driven immune responses.
Nakanishi
K
K
Department of Immunology and Medical Zoology, Hyogo College of Medicine, 1-1, Mukogawa-cho, Nishinomiya, Hyogo 663-8501, Japan. nakaken@hyo-med.ac.jp
Yoshimoto
T
T
Tsutsui
H
H
Okamura
H
H
D000818:Animals; D001172:Arthritis, Rheumatoid / Q000276:immunology / Q000503:physiopathology; D003424:Crohn Disease / Q000276:immunology / Q000503:physiopathology; D003922:Diabetes Mellitus, Type 1 / Q000276:immunology / Q000503:physiopathology; D005786:Gene Expression Regulation; D006086:Graft vs Host Disease / Q000276:immunology / Q000503:physiopathology; D006801:Humans; D007371:Interferon-gamma / Q000378:metabolism; D018664:Interleukin-12 / Q000378:metabolism / Q000494:pharmacology; D020382:Interleukin-18 / Q000737:chemistry / Q000494:pharmacology / Q000502:physiology*; D053727:Interleukin-18 Receptor alpha Subunit; D007694:Killer Cells, Natural / Q000276:immunology / Q000378:metabolism; D008107:Liver Diseases / Q000276:immunology / Q000503:physiopathology; D009103:Multiple Sclerosis / Q000276:immunology / Q000503:physiopathology; D018123:Receptors, Interleukin / Q000737:chemistry / Q000378:metabolism*; D053724:Receptors, Interleukin-18; D018417:Th1 Cells / Q000187:drug effects / Q000276:immunology* / Q000378:metabolism; D018418:Th2 Cells / Q000187:drug effects / Q000276:immunology* / Q000378:metabolism
C508572:IL18R1 protein, human; D020382:Interleukin-18; D053727:Interleukin-18 Receptor alpha Subunit; D018123:Receptors, Interleukin; D053724:Receptors, Interleukin-18; D018664:Interleukin-12; D007371:Interferon-gamma