title: Augmented bacterial elimination by Kupffer cells after IL-18 pretreatment via IFN-γ produced from NK cells in burn-injured mice.
abstract: We recently demonstrated that IL-18 injections following burn restored IFN-γ production and increased mouse survival after bacterial infection. However, it has yet to be fully elucidated how the IL-18 therapy affects the function of phagocytic cells. We investigated the effect of IL-18 therapy on function and interaction of Kupffer cells and NK cells in burned mice. C57BL/6 mice received a 20% full-thickness burn, followed by multiple injections with IL-18. Although burn-injured mice had decreased expression of IL-18 receptors on the NK/NKT cells 5 days after injury, multiple IL-18 injections restored this expression. IL-18 treatment also augmented Kupffer cell phagocytosis. Although burn decreased the number of CD68(+) Kupffer cells with phagocytic activity, IL-18 treatment partially restored their proportion, and augmented phagocytosis-induced ROS production in CD68(+) Kupffer cells after the injection of heat-killed Escherichia coli. Consistently, IL-18 restored the impaired E. coli killing activity of Kupffer cells of burn-injured mice. Such Kupffer cell activation by IL-18 was abrogated by the deletion of NK cells or IFN-γ. In conclusion, IL-18 therapy in burn-injured mice enhanced function of CD68(+) Kupffer cells via the activation of liver NK cells and augmentation of their IFN-γ production, thereby improving survival after E. coli infection.
authors.affiliation: Division of Traumatology, National Defense Medical College Research Institute, Tokorozawa, Japan.
authors.forename: Hiromi
authors.initials: H
authors.lastname: Miyazaki
authors.forename: Manabu
authors.initials: M
authors.lastname: Kinoshita
authors.forename: Satoshi
authors.initials: S
authors.lastname: Ono
authors.forename: Masahiro
authors.initials: M
authors.lastname: Nakashima
authors.forename: Etsuko
authors.initials: E
authors.lastname: Hara
authors.forename: Hideki
authors.initials: H
authors.lastname: Ohno
authors.forename: Shuhji
authors.initials: S
authors.lastname: Seki
authors.forename: Daizoh
authors.initials: D
authors.lastname: Saitoh
mesh_terms: D000818:Animals; D002056:Burns / Q000188:drug therapy* / Q000382:microbiology; D004927:Escherichia coli Infections / Q000188:drug therapy*; D007371:Interferon-gamma / Q000096:biosynthesis* / Q000097:blood; D018664:Interleukin-12 / Q000097:blood; D020382:Interleukin-18 / Q000494:pharmacology*; D007694:Killer Cells, Natural / Q000187:drug effects* / Q000378:metabolism; D007728:Kupffer Cells / Q000187:drug effects* / Q000378:metabolism; D007963:Leukocytes, Mononuclear / Q000382:microbiology; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D023421:Models, Animal; D010587:Phagocytosis / Q000187:drug effects; D011518:Proto-Oncogene Proteins / Q000378:metabolism; D020794:Receptor Protein-Tyrosine Kinases / Q000378:metabolism; D053724:Receptors, Interleukin-18 / Q000378:metabolism
chemical_list: D020382:Interleukin-18; D011518:Proto-Oncogene Proteins; D053724:Receptors, Interleukin-18; D018664:Interleukin-12; D007371:Interferon-gamma; D020794:Receptor Protein-Tyrosine Kinases; C483813:Ros1 protein, mouse