Pathophysiological roles of interleukin-18 in inflammatory liver diseases

• Published in: Immunological reviews Vol. 174; no. 1; pp. 192 - 209
• Main Authors: Tsutsui, Hiroko, Matsui, Kiyoshi, Okamura, Haruki, Nakanishi, Kenji
• Format: Journal Article
• Language: English
• Published: Copenhagen Munksgaard International Publishers 01.04.2000
• Subjects: Animals; Apoptosis; Caspase 1 - physiology; Cercopithecus aethiops; COS Cells; Cytotoxicity, Immunologic - drug effects; Disease Models, Animal; Drosophila Proteins; Endopeptidases - physiology; Endotoxemia - immunology; Endotoxemia - physiopathology; Enzyme Activation; Fas Ligand Protein; fas Receptor - physiology; Glycoproteins - physiology; Hepatitis - immunology; Hepatitis - physiopathology; Hepatitis, Animal - chemically induced; Hepatitis, Animal - physiopathology; Hepatitis, Viral, Animal - immunology; Hepatitis, Viral, Animal - physiopathology; Hepatitis, Viral, Human - immunology; Hepatitis, Viral, Human - physiopathology; Humans; Insect Proteins - physiology; Intercellular Signaling Peptides and Proteins; Interferon-gamma - physiology; Interleukin-18 - biosynthesis; Interleukin-18 - deficiency; Interleukin-18 - physiology; Interleukin-18 Receptor alpha Subunit; Kupffer Cells - physiology; Lipopolysaccharides - toxicity; Membrane Glycoproteins - physiology; Mice; Mice, Knockout; Propionibacterium acnes - immunology; Rats; Receptors, Cell Surface; Receptors, Interleukin - physiology; Receptors, Interleukin-18; Signal Transduction; Toll-Like Receptors; Transfection
• ISSN: 0105-2896; 1600-065X
• DOI: 10.1034/j.1600-0528.2002.017418.x

Innate immune response to microbes sometimes determines the nature of the following specific immune response. Kupffer cells, a potent constituent of innate immunity, play a key role in developing the type 1 immune response by interleukin (IL)-12 production. Furthermore, Kupffer cells have the potential to induce liver injury by production of IL-18. Propionibacterium acnes-primed lipopolysaccharide (LPS)-challenged liver injury is the prototype of IL-18-induced tissue injury, in which IL-18 acts on natural killer cells to increase Fas ligand (FasL) that causes liver injury by induction of Fas-dependent hepatocyte apoptosis. LPS induces IL-18 secretion from Kupffer cells in a caspase-1-dependent manner. Indeed, caspase-1-deficient mice are resistant to P. acnes and LPS-induced liver injury. However, administration of soluble FasL induces acute liver injury in P. acnes-primed caspase-1-deficient mice but does not do so in IL-18-deficient mice, indicating that IL-18 release in a caspase-1-independent fashion is essential for this liver injury. Therefore, a positive feedback loop between FasL and IL-18 plays an important role in the pathogenesis of endotoxin-induced liver injury.