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

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.

Rats were divided into five groups: the S group, sham-operation; the SG group, sham-operation followed by intravenous gadolinium chloride (GdCl(3): 7 mg/kg) administration to inhibit Kupffer cell function; the H group, two-thirds hepatectomy; the HG group, hepatectomy and subsequent GdCl(3) administration; the HGS group, hepatectomy and splenectomy with GdCl(3) administration. Lipopolysaccharide (1.5 mg/kg) was intravenously administered for each group 48 h after surgery.

GdCl(3) treatment significantly suppressed the elevation of plasma tumor necrosis factor (TNF)-alpha levels by lipopolysaccharide administration with completely inhibited induction of hepatic TNF-alpha 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-alpha/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.

Kupffer cells after hepatectomy may aggravate endotoxin-induced liver injury via down-regulation of IL-10 production in the spleen.