Hepatocyte function in sepsis: Kupffer cells mediate a biphasic protein synthesis response in hepatocytes after exposure to endotoxin or killed Escherichia coli.

Alterations in hepatic function are seen in sepsis and/or multiple system organ failure. We hypothesized that Kupffer cells (KC) within the liver may mediate functional alterations in adjacent hepatocytes (HC) in response to bacterial products. We have previously described decreases in rat HC protein synthesis during in vitro cocultivation with peritoneal macrophages in the presence of gentamicin-killed Escherichia coli (GKEC) or endotoxin (LPS). The present studies demonstrate that purified (greater than 95%), syngeneic, or allogeneic KC exposed to GKEC or LPS impart a biphasic response in cultured HC. When HC were cultured alone there was no alteration in 3H-leucine incorporation into HC protein after the addition of GKEC or LPS. When HC were cocultured with KC there was increased protein synthesis compared with HC alone (p less than 0.001). After the addition of GKEC or LPS there was an immediate increase in coculture HC protein synthesis. However, a marked decrease in coculture protein synthesis was seen 16 degrees later (p less than 0.001). To ensure that KC alone were responsible, splenic lymphocytes were added to HC alone or HC/KC coculture, but they did not alter the results. HC viability and appearance were unchanged throughout the experiments. These results show that exposure of KC to microbial products can profoundly alter HC function and support the concept of local KC modulation of HC function during sepsis.