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.

Abstract

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.

• Authors: Katsunori Ami, Manabu Kinoshita, Akira Yamauchi, Tetsuro Nishikage, Yoshiko Habu, Nariyoshi Shinomiya, Takehisa Iwai, Hoshio Hiraide, Shuhji Seki
• Journal: Journal of immunology (Baltimore, Md. : 1950) (J Immunol) Vol. 169 Issue 8 Pg. 4437-42 (Oct 15 2002) ISSN: 0022-1767 [Print] United States
• PMID: 12370378 (Publication Type: Journal Article)

Chemical References

• Interleukin-18
• Lipopolysaccharides
• Interleukin-10
• Interferon-gamma

Topics

• 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)