Liver nonparenchymal cells are stimulated to provide interleukin 6 for induction of the hepatic acute-phase response in endotoxemia but not in remote localized inflammation
T. R. Billiar, R. D. Curran, D. L. Williams and P. H. Kispert
Department of Surgery, University of Pittsburgh, PA 15261.
It has been postulated that Kupffer cells provide signals that regulate
hepatocyte responses in sepsis and inflammation. Although in vitro data
support such a hypothesis, to our knowledge, no in vivo evidence has been
reported. We injected rats with lipopolysaccharide intraperitoneally to
simulate sepsis or turpentine intramuscularly to mimic localized
inflammation. Both treatments are known to induce the hepatic acute-phase
response. Liver nonparenchymal cells and hepatocytes were isolated and
placed in culture. Hepatocyte fibrinogen synthesis was measured as an
indication of interleukin 6 exposure, while nonparenchymal interleukin 6
production was measured directly. Both lipopolysaccharide and turpentine
stimulated a sharp increase in hepatocyte fibrinogen synthesis (turpentine
greater than lipopolysaccharide). However, only lipopolysaccharide
injection was associated with increased nonparenchymal cell interleukin 6
synthesis. Increased circulating levels of interleukin 6 could be found
only after lipopolysaccharide injection. In addition, tumor necrosis factor
synthesis was enhanced by lipopolysaccharide but not turpentine. Our data
show that nonparenchymal cells are stimulated to provide the interleukin 6
signal to hepatocytes in endotoxemia but not in remote localized
inflammation, even though both treatments stimulate the hepatic acute-phase
response. Our findings support paracrine functions for liver sinusoidal
cells in certain septic states.
