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Interleukin-10 inhibits hepatic injury and tumor necrosis factor-alpha and interferon-gamma mRNA expression induced by staphylococcal enterotoxin B or lipopolysaccharide in galactosamine-sensitized mice

J Hepatol. 1999 Nov;31(5):815-24. doi: 10.1016/s0168-8278(99)80282-7.

Abstract

Background/aims: Proinflammatory cytokines including tumor necrosis factor alpha (TNF-alpha) and interferon gamma (IFN-gamma) play a critical role in the pathogenesis of liver injury induced by lipopolysaccharide (LPS) or staphylococcal enterotoxin B (SEB) in D-galactosamine (GalN)-sensitized mice. The aim of this study was to examine the ability of interleukin-10 (IL-10), a recently characterized, highly potent anti-inflammatory mediator, to protect sensitized mice against hepatotoxicity induced by SEB or LPS.

Methods: IL-10 was injected at various concentrations into BALB/c mice treated by GalN/SEB or GalN/LPS. Liver injury was assessed biochemically and histologically. Serum levels of TNF-alpha and IFN-gamma were measured and the expressions of TNF-alpha and IFN-gamma mRNA in the liver and spleen were determined by reverse-transcription polymerase chain reaction.

Results: Treatment with IL-10 markedly reduced serum transaminase activities in a dose-dependent manner and reduced hemorrhagic liver damage in sensitized mice exposed to either toxin. IL-10 also inhibited increases in serum TNF-alpha and IFN-gamma concentrations with either toxin. Treatment with IL-10 significantly reduced TNF-alpha mRNA and IFN-gamma mRNA expression in the liver and spleen after administration of either toxin to sensitized mice.

Conclusions: These findings suggest that IL-10 is capable of regulating both T cell- and macrophage-mediated hepatic injury in vivo and that this cytokine might be useful in the treatment of acute liver failure.

MeSH terms

  • Animals
  • Cells, Cultured
  • Enterotoxins / toxicity*
  • Galactosamine / toxicity*
  • Gene Expression Regulation / drug effects
  • Gene Expression Regulation / immunology*
  • Interferon-gamma / blood
  • Interferon-gamma / genetics*
  • Interleukin-10 / pharmacology*
  • Lipopolysaccharides / toxicity*
  • Liver / drug effects*
  • Liver / immunology
  • Liver / pathology
  • Male
  • Mice
  • Mice, Inbred BALB C
  • RNA, Messenger / genetics
  • Spleen / drug effects
  • Spleen / immunology
  • Spleen / pathology
  • Superantigens / toxicity
  • Transcription, Genetic / drug effects
  • Transcription, Genetic / immunology*
  • Tumor Necrosis Factor-alpha / genetics*

Substances

  • Enterotoxins
  • Lipopolysaccharides
  • RNA, Messenger
  • Superantigens
  • Tumor Necrosis Factor-alpha
  • Interleukin-10
  • enterotoxin B, staphylococcal
  • Galactosamine
  • Interferon-gamma