Induction of CINC (interleukin-8) production in rat liver by non-parenchymal cells

The production of interleukin-8 (CINC: cytokine-induced neutrophil chemo-attractant) from different cell populations in the rat liver was studied and cells related to the initiation of CINC production in lipopolysaccharide (LPS)-injected endotoxaemic rats were characterized. Sinusoidal endothelial cells (16.4 +/- 10.6 ng/mL) produced significantly higher amounts of CINC in 24 h primary cultures compared with hepatocytes (0.9 +/- 0.9 ng/mL; P < 0.05) and Kupffer cells (6.5 +/- 5.1 ng/mL; P < 0.05). Lipopolysaccharide, tumour necrosis factor-alpha (TNF-alpha), and interleukin-1 alpha (IL-1 alpha) stimulated different liver cell populations to produce CINC; LPS mainly stimulated Kupffer cells. TNF-alpha stimulated hepatocytes and IL-1 alpha stimulated all three types of cells. Intraperitoneal injection of LPS (4 mg/kg) caused CINC accumulation in non-parenchymal cells of the rat liver within 1 h of injection, as shown by immunohistochemical staining. In contrast, CINC-positive hepatocytes were not seen until 3 h after injection of LPS. Ethanol was not a direct inducer of CINC production by rat hepatocytes in vitro. These findings strongly suggest that non-parenchymal liver cells, including sinusoidal endothelial cells, are the main source of CINC. Our data also suggest that during endotoxaemia, CINC production is initiated by non-parenchymal cells and this is followed by production from hepatocytes.