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.
OBJECTIVE
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.
Nagaki
M
M
First Department of Internal Medicine, Gifu University School of Medicine, Japan.
Tanaka
M
M
Sugiyama
A
A
Ohnishi
H
H
Moriwaki
H
H
D000818:Animals; D002478:Cells, Cultured; D004768:Enterotoxins / Q000633:toxicity*; D005688:Galactosamine / Q000633:toxicity*; D005786:Gene Expression Regulation / Q000187:drug effects / Q000276:immunology*; D007371:Interferon-gamma / Q000097:blood / Q000235:genetics*; D016753:Interleukin-10 / Q000494:pharmacology*; D008070:Lipopolysaccharides / Q000633:toxicity*; D008099:Liver / Q000187:drug effects* / Q000276:immunology / Q000473:pathology; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D012333:RNA, Messenger / Q000235:genetics; D013154:Spleen / Q000187:drug effects / Q000276:immunology / Q000473:pathology; D018089:Superantigens / Q000633:toxicity; D014158:Transcription, Genetic / Q000187:drug effects / Q000276:immunology*; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics*
D004768:Enterotoxins; D008070:Lipopolysaccharides; D012333:RNA, Messenger; D018089:Superantigens; D014409:Tumor Necrosis Factor-alpha; D016753:Interleukin-10; C031818:enterotoxin B, staphylococcal; D005688:Galactosamine; D007371:Interferon-gamma