title: Role of interleukin-18 in intrahepatic inflammatory cell recruitment in acute liver injury.
abstract: Although the innate immune system has been demonstrated to play important roles as the first line of defense against various infections, little is known about the interactions between intrahepatic inflammatory cells and the cytokine network in the liver. Here, we examined the role of IL-18 in IHL recruitment in acute liver injury. C57BL/6 mice were injected with an αCD40 mAb, and their serum IL-18 levels were observed to increase, with subsequent recruitment of IHLs into the liver. NKT cells were involved in this liver injury, as the serum ALT levels were reduced in NKT KO mice through the suppression of macrophage and monocyte migration and cytokine production. In contrast, depletion of neutrophils exacerbated the liver injury associated with high levels of TNF-α and IL-18 and increased numbers of macrophages and monocytes. Treatment with a neutralizing antibody against IL-18 reduced the serum ALT levels and inflammatory cell accumulation in the liver. Finally, additional administration of rIL-18 with αCD40 injection caused severe liver injury with increased IFN-γ production by NK cells. In conclusion, these findings demonstrate that IL-18 modulates liver inflammation by the recruitment of inflammatory cells, including NKT cells, macrophages, monocytes, and neutrophils.
authors.affiliation: Division of Hepatology, Tokyo Metropolitan Cancer and Infectious Diseases Center, Komagome Hospital, 18-22-3 Honkomagome, Bunkyo-ku, Tokyo 113-8677, Japan. kkimura@cick.jp
authors.forename: Kiminori
authors.initials: K
authors.lastname: Kimura
authors.forename: Satoshi
authors.initials: S
authors.lastname: Sekiguchi
authors.forename: Seishu
authors.initials: S
authors.lastname: Hayashi
authors.forename: Yukiko
authors.initials: Y
authors.lastname: Hayashi
authors.forename: Tsunekazu
authors.initials: T
authors.lastname: Hishima
authors.forename: Masahito
authors.initials: M
authors.lastname: Nagaki
authors.forename: Michinori
authors.initials: M
authors.lastname: Kohara
mesh_terms: D000818:Animals; D019013:CD40 Antigens; D002454:Cell Differentiation; D002465:Cell Movement; D049109:Cell Proliferation; D007150:Immunohistochemistry; D007249:Inflammation / Q000276:immunology / Q000473:pathology*; D007267:Injections; D007371:Interferon-gamma / Q000378:metabolism; D020382:Interleukin-18 / Q000097:blood / Q000276:immunology*; D008099:Liver / Q000276:immunology* / Q000473:pathology*; D008264:Macrophages / Q000166:cytology; D051379:Mice; D008810:Mice, Inbred C57BL; D055611:Natural Killer T-Cells / Q000276:immunology; D009500:Neutralization Tests; D009504:Neutrophils / Q000276:immunology; D051381:Rats
chemical_list: D019013:CD40 Antigens; D020382:Interleukin-18; D007371:Interferon-gamma