Kupffer cells modulate splenic, interleukin-10 production in endotoxin-induced liver injury after partial hepatectomy.

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Background : This study was conducted to investigate the implication of Kupffer cells and the spleen in interleukin (IL)-10 production in endotoxin-induced liver injury after hepatectomy.Materials and Methods : Rats were divided into five groups : the S group, sham-operation ; the SG group, sham-operation followed by intravenous gadolinium chloride (GdCl3 : 7mg/kg) administration to inhibit Kupffer cell function ; the H group, two-thirds hepatectomy ; the HG group, hepatectomy and subsequent GdCl3 administration ; the HGS group, hepatectomy and splenectomy with GdCl3 administration.Lipopolysaccharide (1.5mg/kg) was intravenously administered for each group 48 hours after surgery. Results : GdCl3 treatment significantly suppressed the elevation of plasma alanine aminotransferase and tumor necrosis factor (TNF)-a by lipopolysaccharide administration, and completely inhibited the induction of hepatic tissue TNF-a and IL-10 mRNAs. In the HG group, plasma IL-10 levels were significantly higher than those in the H and HGS groups and splenic IL-10 mRNA was markedly enhanced 1 hour after lipopolysaccharide administration. Plasma TNF-a /IL-10 ratio was higher in the rank order H>HGS>HG. The 24-hour mortality (H group, 67% ; HGS group, 33% ; HG group, 20%) and hepatic parenchymal damage was in the same order. Conclusion : Kupffer cells after hepatectomy may aggravate endotoxin-induced liver injury via down-regulation of IL-10 production in the spleen.