Rat hepatocytes and kupffer cells interact to produce interleukin-8
(cinc) in the setting of ethanol1,2.
Maher, Jacquelyn J.
Liver Core Center and Department of Medicine, University of
California, San Francisco, San Francisco General Hospital
APStracts 2:0088G, 1995.
Interleukin-8 is a neutrophil chemoattractant that has been implicated
in the pathogenesis of alcoholic hepatitis. The mechanism of ethanol
-induced interleukin-8 production in liver is uncertain, although
hepatocytes and Kupffer cells have both been proposed as sources of
the chemokine. In this study we investigated whether short-term
ethanol exposure stimulates production of rat interleukin-8 (CINC) by
normal rat hepatocytes and Kupffer cells in primary culture. Initial
experiments verified that hepatocytes and Kupffer cells produce CINC
in response to cytokines or lipopolysaccharide. Ethanol, by contrast,
failed to stimulate CINC secretion by either cell type even at
concentrations as high as 100 mM. Although ethanol had no direct
effect on liver cell CINC production, conditioned medium from
ethanol-treated hepatocytes induced a 3-fold rise in CINC production
by Kupffer cells. The increase was abrogated when hepatocytes were
treated with ethanol and the metabolic inhibitor 4-methylpyrazole.
The results suggest that the mechanism of ethanol-induced CINC
production is indirect, involving ethanol oxidation and communication
between hepatocytes and Kupffer cells.
Received 27 December 1994; accepted in final form 29 April 1995.
APS Manuscript Number G499-4.
Article publication pending Am. J. Physiol. (Gastrointest. Liver
Physiology).
ISSN 1080-4757 Copyright 1995 The American Physiological Society.
Published in APStracts on 9 May 1995.