Immunosuppressive Effect of Alcohol on Hepatic Parenchymal and Nonparenchymal Cell Functions Following Endotoxin
Alcoholism has long been associated with an increased frequency and severity of infection (1). Several aspects of host defense are altered by chronic alcohol abuse, but even the acute ingestion of ethanol has demonstrable deleterious effects on humoral and cell-mediated immunity (2,3). Furthermore, ethanol has been shown to alter the function of Kupffer cells which are located within the lumen of the liver sinusoids and constitute the majority of the fixed tissue macrophages of the reticuloendothelial system. These cells are highly phagocytic and play an essential role in defense mechanisms against infection by removing immune complexes, viruses, bacteria and bacterial endotoxins from the blood (4,5). The concentration of systemic, circulating endotoxin in alcoholics has been reported to be elevated above basal levels by several investigators (5,6,7). Because gut-derived endotoxins are normally cleared by the liver on the first pass, these data suggest that alcohol impairs the clearance of endotoxin. In addition, ethanol has been shown to impair Kupffer cell function as evidenced by the depressed clearance of microaggregated albumin and endotoxin from the circulation of rats (8). Kupffer cells also secrete a number of cytokines and paracrine substances that modulate both immune function and cellular metabolism (4,9). Several reports indicate that ethanol, both in vivo and in vitro, can decrease the production and/or release of these agents (9,10). Thus, ethanol may modulate the immunologic responses of Kupffer cells by affecting both phagocytosis and secretory processes of these cells.
KeywordsGlucose Uptake Kupffer Cell Superoxide Anion Generation Ethanol Administration Hepatic Gluconeogenesis
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