Multiple Systems Organ Failure

TLDR

The cause of liver failure in MSOF syndrome remains unknown. The study examines whether Kupffer cell–mediated modulation of hepatocyte function contributes to MSOF‑associated liver failure. Rat hepatocytes were cultured and protein synthesis measured, then co‑cultured with Kupffer cell–rich nonparenchymal cells ± endotoxin to assess effects on synthesis. Co‑culture of Kupffer cells with endotoxin markedly suppressed hepatocyte protein synthesis, indicating that endotoxin‑stimulated Kupffer cells may underlie hepatic insufficiency in MSOF.

Abstract

The etiology of hepatic insufficiency associated with the multiple systems organ failure (MSOF) syndrome is unclear. The authors have investigated the possibility that a macrophage/ Kupffer cell mediated modulation of hepatocyte function may play a role in this phenomenon. Isolated rat hepatocytes were cultured, and their rate of protein synthesis was measured by cpm of 3H leucine incorporation into protein. Nonparenchymal rat liver cells (NPC) comprised of 35-40% Kupffer cells were added to hepatocytes to establish a co-culture with or without endotoxin. Neither NPC alone nor endotoxin alone affected hepatocyte protein synthesis. However, in the presence of endotoxin, NPC caused a marked diminution of hepatocyte protein synthesis (4,396 ± 449 cpm) compared with control hepatocytes (10,943 ± 623 cpm). No change in microscopic morphology or ability to exclude trypan blue occurred. This modulation of hepatocyte function by an endotoxin stimulated Kupffer cell preparation may, in part, represent the mechanism of hepatic insufficiency associated with the MSOF syndrome.