IFN-gamma production from liver mononuclear cells of mice in burn injury as well as in postburn bacterial infection models and the therapeutic effect of IL-18.
Hosts after severe burn injury are known to have a defect in the Th1 immune response and are susceptible to bacterial infections. We herein show that liver NK cells are potent IFN-gamma producers early after burn injury. However, when mice were injected with LPS 24 h after burn injury, IFN-gamma production from liver mononuclear cells (MNC; which we previously showed to be NK cells) was suppressed, and the serum IFN-gamma concentration did not increase, while serum IL-10 conversely increased compared with control mice. Interestingly, a single injection of IL-18 simultaneously with LPS greatly restored the serum IFN-gamma concentration in mice with burn injury and also increased IFN-gamma production from liver MNC. Nevertheless, a single IL-18 injection into mice simultaneously with LPS was no longer effective in the restoration of serum IFN-gamma and IFN-gamma production from the liver MNC at 7 days after burn injury, when mice were considered to be the most immunocompromised. However, IL-18 injections into mice on alternate days beginning 1 day after burn injury strongly up-regulated LPS-induced serum IFN-gamma levels and IFN-gamma production from liver and spleen MNC of mice 7 days after burn injury and down-regulated serum IL-10. Furthermore, similar IL-18 therapy up-regulated serum IFN-gamma levels in mice with experimental bacterial peritonitis 7 days after burn injury and greatly decreased mouse mortality. Thus, IL-18 therapy restores the Th1 response and may decrease the susceptibility to bacterial infection in mice with burn injury.
Ami
Katsunori
K
Division of Basic Traumatology, National Defense Medical College Research Institute, Namiki 3-2, Tokorozawa 359-8513, Japan.
Kinoshita
Manabu
M
Yamauchi
Akira
A
Nishikage
Tetsuro
T
Habu
Yoshiko
Y
Shinomiya
Nariyoshi
N
Iwai
Takehisa
T
Hiraide
Hoshio
H
Seki
Shuhji
S
D000818:Animals; D001424:Bacterial Infections / Q000209:etiology / Q000276:immunology* / Q000401:mortality / Q000628:therapy; D002056:Burns / Q000150:complications / Q000276:immunology* / Q000628:therapy; D002478:Cells, Cultured; D015536:Down-Regulation / Q000276:immunology; D004334:Drug Administration Schedule; D007274:Injections, Intraperitoneal; D007275:Injections, Intravenous; D007371:Interferon-gamma / Q000096:biosynthesis* / Q000097:blood; D016753:Interleukin-10 / Q000037:antagonists & inhibitors / Q000096:biosynthesis; D020382:Interleukin-18 / Q000008:administration & dosage / Q000627:therapeutic use*; D007694:Killer Cells, Natural / Q000276:immunology* / Q000378:metabolism*; D008070:Lipopolysaccharides / Q000008:administration & dosage / Q000037:antagonists & inhibitors; D008099:Liver / Q000166:cytology / Q000276:immunology* / Q000378:metabolism*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D010538:Peritonitis / Q000209:etiology / Q000276:immunology / Q000401:mortality / Q000628:therapy; D013154:Spleen / Q000166:cytology / Q000276:immunology / Q000378:metabolism; D017211:Treatment Failure; D015854:Up-Regulation / Q000276:immunology
D020382:Interleukin-18; D008070:Lipopolysaccharides; D016753:Interleukin-10; D007371:Interferon-gamma