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

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 SEE 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.