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.
AuthorsKatsunori Ami, Manabu Kinoshita, Akira Yamauchi, Tetsuro Nishikage, Yoshiko Habu, Nariyoshi Shinomiya, Takehisa Iwai, Hoshio Hiraide, Shuhji Seki
JournalJournal of immunology (Baltimore, Md. : 1950) (J Immunol) Vol. 169 Issue 8 Pg. 4437-42 (Oct 15 2002) ISSN: 0022-1767 [Print] United States
PMID12370378 (Publication Type: Journal Article)
Chemical References
  • Interleukin-18
  • Lipopolysaccharides
  • Interleukin-10
  • Interferon-gamma
  • Animals
  • Bacterial Infections (etiology, immunology, mortality, therapy)
  • Burns (complications, immunology, therapy)
  • Cells, Cultured
  • Down-Regulation (immunology)
  • Drug Administration Schedule
  • Injections, Intraperitoneal
  • Injections, Intravenous
  • Interferon-gamma (biosynthesis, blood)
  • Interleukin-10 (antagonists & inhibitors, biosynthesis)
  • Interleukin-18 (administration & dosage, therapeutic use)
  • Killer Cells, Natural (immunology, metabolism)
  • Lipopolysaccharides (administration & dosage, antagonists & inhibitors)
  • Liver (cytology, immunology, metabolism)
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Peritonitis (etiology, immunology, mortality, therapy)
  • Spleen (cytology, immunology, metabolism)
  • Treatment Failure
  • Up-Regulation (immunology)

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