We investigated the pathogenesis of septic liver injury in rats caused by cecal ligation and puncture. In this model, numerous neutrophils accumulated in the liver in parallel with the development of liver dysfunction. The supernatants of hepatic macrophages isolatedfrom these septic rats 24 hr after cecal ligation and puncture had enhanced chemotactic activities for human neutrophils. These results suggest that in sepsis, hepatic macrophages attract neutrophils to the liver. Human neutrophils preincubated in this macrophage supernatant had the following biological activities not seen in the sham-operated controls. (a) They became more adherent to cultured endothelial cells through up-regulation of adhesion molecules such as CDllb/CDl8, (b) their chemiluminescence was markedly elevated. These functional changes of cecal ligation and puncture hepatic macrophages were the same as those in endotoxin-pretreated hepatic macrophages after isolation from normal rats. Therefore we suspect that hepatic macrophages are activated by portal vein endotoxin in sepsis. These activated hepatic macrophages secreted chemical mediators of inflammation, including leukotriene B, and tumor necrosis factor. In conclusion, hepatic macrophages seem to interact closely with neutrophils and play an important role in the pathogenesis of septic liver injury. (HEPATOLOGY 1993;17:1086-1094.) Endotoxicosis and sepsis are accompanied by severe impairment of liver function, which frequently progresses to fatal multiple organ failure (1, 2). The mortality rate of this condition remains unacceptably high despite the various therapeutic interventions that have been developed.
The pathogenesis of this septic liver injury has been investigated extensively; however, many features await clarification.
On one hand, many researchers have focused their studies on changes in neutrophil function because large numbers of neutrophils are known to accumulate in