ROLE OF KUPFFER CELLS AND THE SPLEEN IN MODULATION OF ENDOTOXIN-INDUCED LIVER-INJURY AFTER PARTIAL-HEPATECTOMY

The hypothesis that both activated Kupffer cells and the spleen may be responsible for endotoxin-induced liver injury following partial hepa tectomy was investigated. Male rats were divided into a sham group rec eiving laparotomy alone and three groups receiving a two-thirds hepate ctomy; one group was given normal saline (NS) solution as a vehicle co ntrol, one group received intravenous gadolinium chloride (GC group) ( 7 mg/kg body weight) for 2 days before intravenous injection of endoto xin to inhibit Kupffer cell phagocytosis, and the third group simultan eously underwent splenectomy and partial hepatectomy (SH group), As en dotoxin, lipopolysaccharide (LPS) (1 mg/kg body weight) was administer ed intravenously 2 days after surgery, In the GC and SH groups, phagoc ytic activity was reduced to approximately 40% of that in the sham gro up, The highest plasma tumor necrosis factor alpha (TNF-alpha) level ( 8,544 +/- 1,223 pg/mL) was observed in the NS group at 1 hour after LP S administration, and the level was significantly reduced by GdCl3 or splenectomy (P < 0.05), Inhibition of Kupffer cell function and splene ctomy attenuated functional and structural liver damage associated wit h the decreased hepatic infiltration of polymorphonuclear leukocytes ( PMNs) and reduced priming of circulating PMNs in the early stage of en dotoxemia following partial hepatectomy, Consequently, the 24-hour sur vival rate of the SH and GC groups was significantly improved to 50% a nd 80%, respectively (P < .05), while that of the NS group was 12.5%. These findings indicate that the modification of inflammatory mediator generation by splenectomy or inhibition of Kupffer cell function may be beneficial for the prevention of endotoxin-induced liver injury aft er partial hepatectomy.