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

Abstract

Background/Aims: 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.Methods: Rats were divided into five groups: the S group, sham-operation; the SG group, sham-operation followed by intravenous gadolinium chloride (GdCl3: 7 mg/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 (1.5 mg/kg) was intravenously administered for each group 48 h after surgery.Results: GdCl3 treatment significantly suppressed the elevation of plasma tumor necrosis factor (TNF)-α levels by lipopolysaccharide administration with completely inhibited induction of hepatic TNF-α and IL-10 mRNAs. In the HG group, marked increase in plasma IL-10 levels associated with enhanced splenic IL-10 mRNA was observed 1 h after lipopolysaccharide administration when compared to those in the H and HGS groups. Plasma TNF-α/IL-10 ratio 1 h after lipopolysaccharide administration was higher in the order of H, HGS and HG groups. Hepatic parenchymal damage and the 24-h mortality were lowest in group HG, followed by groups HGS and H.Conclusions: Kupffer cells after hepatectomy may aggravate endotoxin-induced liver injury via down-regulation of IL-10 production in the spleen.