ENDOTOXIN-INDUCED LIVER-INJURY AFTER EXTENDED HEPATECTOMY AND THE ROLE OF KUPFFER CELLS IN THE RAT

Liver injury by endotoxin given during regeneration following a 70% he patectomy was examined in Wistar rats. The intravenous administration of endotoxin caused an elevation of the serum GPT level, and severe da mage of the remnant liver showing centrilobular necrosis with microthr ombi. The highest mortality was induced by the administration of endot oxin to rats 24 h after hepatectomy. Kupffer cells in the regenerative phase of the liver showed an augmented in vitro production of both tu mor necrosis factor (TNF) and interleukin-1 (IL-1). The simultaneous a dministration of heparin and prostagladin E1 (PGE1), which is known to suppress the production of TNF and IL-1, reduced the magnitude of liv er injury and the mortality of these rats. The absence of any direct c ytotoxic effect of TNF and IL-1 against liver cells suggested that the cytokines, produced by Kupffer cells, play an important but indirect role in the remnant liver injury induced by endotoxin after hepatectom y.