Augmented bacterial elimination by Kupffer cells after IL-18 pretreatment via IFN-gamma produced from NK cells in burn-injured mice

作者：Miyazaki Hiromi; Kinoshita Manabu^*; Ono Satoshi; Nakashima Masahiro; Hara Etsuko; Ohno Hideki; Seki Shuhji; Saitoh Daizoh

来源：Burns, 2011, 37(7): 1208-1215.

DOI：10.1016/j.burns.2011.04.010

• Phagocytosis
• Reactive oxygen species
• Post-burn infection
• CD68(+) Kupffer cells

We recently demonstrated that IL-18 injections following burn restored IFN-gamma 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 NM/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-gamma. In conclusion, IL-18 therapy in burn-injured mice enhanced function of CD68(+) Kupffer cells via the activation of liver NM cells and augmentation of their IFN-gamma production, thereby improving survival after E. coli infection.

• 出版日期2011-11