The liver lobule contains parenchymal cells (hepatothe liver during accumulation of neutrophils, the recytes) and four types of nonparenchymal cells, i.e., lease of cytokine-induced neutrophil chemoattractant Kupffer cells, fat-storing cells (lipocytes, Ito cells), en-(CINC) (interleukin-8 [IL-8] related protein in rodents) dothelial cells, and pit cells (organ-associated natural by hepatocytes was investigated in the presence of Kupfkiller cells). Recent studies have shown various roles fer cell-conditioned medium in vitro. Kupffer cells were of these cells in the pathogenesis of liver disease. 1 Alprepared by perfusion of rat liver with collagenase folthough depressed Kupffer cell function has been relowed by centrifugation on a metrizamide gradient and ported in alcoholic liver disease, 2 a recent study showed were cultured in the presence or absence of lipopolysacthat acute alcoholic ingestion causes an increased numcharide (LPS). The conditioned medium was collected ber of Kupffer cells with ultrastructural features of acafter 24 hours, and rat hepatocytes were cultured in the presence or absence of Kupffer cell-conditioned metivation. 3
dium. An amount of CINC in the culture supernatant
In severe acute alcoholic hepatitis, the plasma levels was measured by western blotting analysis and enzymeof endotoxin and several kinds of cytokines such as linked immunosorbent assay (ELISA), and expression of interleukin 1 (IL-1), tumor necrosis factor a (TNF-a), its messenger RNA (mRNA) was assessed by the polyand IL-8 are reported to be increased. Neutrophil merase chain reaction. LPS-stimulated Kupffer cellaccumulation observed around sites of hepatocyte neconditioned medium enhanced an expression of CINC crosis is a characteristic feature of severe alcoholic mRNA in hepatocytes and increased the production of hepatitis. Although the mechanism of neutrophil ac-CINC by hepatocytes. Enhanced production of CINC was cumulation in the liver of alcoholics has not yet not shown when the Kupffer cell-conditioned medium was pretreated with heat (56ะC, 30 minutes). The producbeen clarified, rat hepatocyte production of IL-8 (cytotion of CINC by hepatocytes in the presence of the LPSkine-induced neutrophil chemoattractant in rodents stimulated Kupffer cell-conditioned medium was re-[CINC]) is increased by chronic ethanol intake in vivo 8 duced by an antibody against interleukin 1b (IL-1b), but or by exposure to ethanol in vitro. 9 Recently, the pronot by antibodies against tumor necrosis factor a (TNFduction of IL-8 has been shown to be regulated by ina) or LPS. These results suggest that production of CINC flammatory cytokines in vitro. 10 Recent studies have by hepatocytes could be regulated by IL-1b released also shown that hepatocyte injury is modulated by from Kupffer cells, leading to neutrophil accumulation Kupffer cells and that these cells are known to produce during liver injury, because this protein is a strong chemoattractant for neutrophils. (HEPATOLOGY 1996;23: several biologically active mediators, including various 353-358.)
kinds of cytokines and toxic substances like oxygenfree radicals and reactive nitrogen. Previous studies have shown that endotoxin administration induces hepatic injury in alcohol-fed rats 13 Abbreviations: IL, interleukin; TNF-a, tumor necrosis factor a; CINC, cytokine-induced neutrophil chemoattractant; LPS, lipopolysaccharide; ELISA, en-and that endotoxemia is common in patients with alcozyme-linked immunosorbent assay; mRNA, messenger RNA; cDNA, compleholic liver disease. Because endotoxin is known to actimentary DNA.