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


RESULTS
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.


CONCLUSIONS
Kupffer cells after hepatectomy may aggravate endotoxin-induced liver injury via down-regulation of IL-10 production in the spleen.
Kurachi
Kiyotaka
K
Second Department of Surgery, Hamamatsu University School of Medicine, 1-20-1 Handayama, Hamamatsu 431-3192, Japan.
Suzuki
Shohachi
S
Sakaguchi
Takanori
T
Yokoi
Yoshihiro
Y
Konno
Hiroyuki
H
Baba
Satoshi
S
Nakamura
Satoshi
S
D000410:Alanine Transaminase / Q000097:blood; D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology; D005682:Gadolinium / Q000494:pharmacology; D015870:Gene Expression / Q000276:immunology; D006498:Hepatectomy; D016753:Interleukin-10 / Q000097:blood / Q000235:genetics*; D007728:Kupffer Cells / Q000187:drug effects / Q000276:immunology* / Q000473:pathology; D008070:Lipopolysaccharides / Q000494:pharmacology; D008107:Liver Diseases / Q000276:immunology* / Q000401:mortality / Q000473:pathology; D008297:Male; D012333:RNA, Messenger / Q000032:analysis; D051381:Rats; D017208:Rats, Wistar; D013154:Spleen / Q000276:immunology*; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics / Q000378:metabolism
D000893:Anti-Inflammatory Agents; D008070:Lipopolysaccharides; D012333:RNA, Messenger; D014409:Tumor Necrosis Factor-alpha; D016753:Interleukin-10; D005682:Gadolinium; D000410:Alanine Transaminase; C038958:gadolinium chloride