Immunosuppressive Effect of Alcohol on Hepatic Parenchymal and Nonparenchymal Cell Functions Following Endotoxin

  • John J. Spitzer
  • Gregory J. Bagby
  • Abraham P. Bautista
  • Nympha B. D’Souza
  • Patricia E. Molina
  • Charles H. Lang
Part of the Advances in Experimental Medicine and Biology book series (AEMB, volume 288)


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.


Glucose Uptake Kupffer Cell Superoxide Anion Generation Ethanol Administration Hepatic Gluconeogenesis 


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. 1.
    H. G. Adam and C. Jordan, Infections in the alcoholic, Med. Clin. N. Am. 68:179 (1984).Google Scholar
  2. 2.
    R. R. MacGregor, Alcohol and immune defense, J. Am. Med. Assoc. 256:-1474 (1986).CrossRefGoogle Scholar
  3. 3.
    C. L. Young and R. R. MacGregor, Alcohol and host defenses: Infectious consequences, Infections Med. Sept: 163 (1989).Google Scholar
  4. 4.
    E. A. Jones and J. A. Summerfield, Kupffer cells, in: “The Liver: Biology and Pathobiology,” I. M. Arias, W. B. Jakoby, H. Popper, D. Schachter, and D. A. Shafritz, eds., Raven Press, New York (1988).Google Scholar
  5. 5.
    J. P. Nolan and D. S. Camara, Endotoxin, sinusoidal cells and liver injury, Prog. Liver Dis. 7:361 (1982).Google Scholar
  6. 6.
    C. Bode, V. Kugler, and J. C. Bode, Endotoxemia in patients with alcoholic and non-alcoholic cirrhosis and in subjects with no evidence of chronic liver disease following acute alcohol excess, J. Hepatol. 4:8 (1987).PubMedCrossRefGoogle Scholar
  7. 7.
    H. Liehr, Endotoxins and alcohol hepatitis, in: “Clinical Hepatology,” G. Cosmos and H. Thaler, eds., Springer Verlag, Berlin (1983).Google Scholar
  8. 8.
    Y. K. Liu, Phagocytic capacity of the reticuloendothelial system in alcoholics, J. Reticuloendoth. Soc. 25:605 (1979).Google Scholar
  9. 9.
    D. Keppler, M. Huber, and T. Baumert, Leukotrienes as mediators in diseases of the liver, Sem. Liver Dis. 8:357 (1988).CrossRefGoogle Scholar
  10. 10.
    N. B. D’Souza, G. J. Bagby, S. Nelson, C. H. Lang, and J. J. Spitzer, Acute alcohol infusion suppresses endotoxin-induced serum tumor necrosis factor, Alcoholism Clin. Exp. Res. 13:295 (1989).CrossRefGoogle Scholar
  11. 11.
    C. H. Lang, G. J. Bagby, and J. J. Spitzer, Glucose kinetics and body temperature after lethal and nonlethal doses of endotoxin, Am. J. Physiol. 248:R471 (1985).PubMedGoogle Scholar
  12. 12.
    C. H. Lang, G. J. Bagby, and J. J. Spitzer, Carbohydrate dynamics in the hypermetabolic septic rat, Metabolism 33:959 (1984).PubMedCrossRefGoogle Scholar
  13. 13.
    N. K. Friedmann, Hormonal regulation of hepatic gluconeogenesis, Physiol. Rev. 64:170 (1984).Google Scholar
  14. 14.
    C. H. Lang, G. J. Bagby, H. L. Blakesley, and J. J. Spitzer, Importance of hyperglucagonemia in eliciting the sepsis-induced increase in glucose production, Circ, Shock 29:181 (1989).Google Scholar
  15. 15.
    R. R. Wolfe, D. Elahi, and J. J. Spitzer, Glucose and lactate kinetics after endotoxin administration in dogs, Am. J. Physiol. 232:E180 (1977).PubMedGoogle Scholar
  16. 16.
    H. A. Krebs, The effects of ethanol on the metabolic activities of the liver, Adv. Enz. Reg. 6:467 (1968).CrossRefGoogle Scholar
  17. 17.
    R. A. Kreisberg, A. M. Siegal, and W. C. Owen, Glucose-lactate interrelationships: Effect of ethanol, J. Clin. Invest. 50:175 (1971).PubMedCrossRefGoogle Scholar
  18. 18.
    A. Lochner, J. Wulff, and L. L. Madison, Ethanol-induced hypoglycemia. I. The acute effects of ethanol on hepatic glucose output and peripheral glucose utilization in fasted dogs, Metabolism 16:1 (1967).PubMedCrossRefGoogle Scholar
  19. 19.
    C. H. Lang, P. E. Molina, G. J. Bagby, and J. J. Spitzer, Chronic alcohol consumption prevents the sepsis-induced increases in gluconeogenesis and metabolic clearance rate, in: “Alcohol, Immunomodulation and AIDS,” Alan R. Liss, New York, (1990).Google Scholar
  20. 20.
    P. E. Molina, C. H. Lang, G. J. Bagby, N..B. D’Souza, and J. J. Spitzer, Ethanol administration diminishes the endotoxin-induced increase in glucose metabolism, Alcoholism Clin. Exp. Res. 13:407 (1989).CrossRefGoogle Scholar
  21. 21.
    N. B. D’Souza, C. H. Lang, G. J. Bagby, and J. J. Spitzer, The effect of ethanol infusion on the altered glucose turnover during bacterial infection, Metabolism 39:588 (1990).PubMedCrossRefGoogle Scholar
  22. 22.
    K. Meszaros, C. H. Lang, G. J. Bagby, and J. J. Spitzer, Contribution of different organs to increased glucose consumption after endotoxin administration, J. Biol. Chem. 262:10965 (1987).PubMedGoogle Scholar
  23. 23.
    A. J. Romanoski, G. J. Bagby, E. L. Bockman, and J. J. Spitzer, Increased muscle glucose uptake and lactate release after endotoxin administration, Am. J. Physiol. 239:311 (1980).Google Scholar
  24. 24.
    S. Seifter and S. Englard, Energy metabolism, in: “The Liver: Biology and Pathobiology,” I. M. Arias, W. B. Jakoby, H. Popper, D. Schachter, D. A. Shafritz, eds., Raven Press, New York, (1988).Google Scholar
  25. 25.
    L. Sokoloff, M. Reivich, C. Kennedy, M. H. Des Rosiers, C. S. Patlak, K. D. Pettingrew, O. Sakurada, and M. Shinohara, The [14C] deoxyglucose method for the measurement of local cerebral glucose utilization, J. Neurochem. 28:897 (1977).PubMedCrossRefGoogle Scholar
  26. 26.
    T. J. C. van Berkel and J. F. Koster, Biochemical characteristics of non-parenchymal liver cells, in: “Kupffer Cells and Other Liver Sinusoidal cells,” E. Wisse and D. L. Knook, eds., Elsevier/North-Holland, Amsterdam, (1977).Google Scholar
  27. 27.
    D. M. Mills and D. Zucker-Franklin, Electron microscopic study of isolated Kupffer cells, Am. J. Path. 54:147 (1969).PubMedGoogle Scholar
  28. 28.
    D. L. Knook and C. H. Slyester, Separation of Kupffer and endothelial cells of the rat liver by centrifugal elutriation, Exp. Cell Res. 99:444 (1976).PubMedCrossRefGoogle Scholar
  29. 29.
    A. J. Sbarra and M. L. Karnovsky, The biochemical basis of phagocytosis, J. Biol. Chem. 234:1355 (1959).PubMedGoogle Scholar
  30. 30.
    A. P. Bautista, K. Meszaros, J. Bojta, and J. J. Spitzer, Superoxide anion generation in the liver during the early state of endotoxemia in rats, J. Leukocyte Biol. 48:123 (1990).PubMedGoogle Scholar

Copyright information

© Plenum Press, New York 1991

Authors and Affiliations

  • John J. Spitzer
    • 1
  • Gregory J. Bagby
    • 1
  • Abraham P. Bautista
    • 1
  • Nympha B. D’Souza
    • 1
  • Patricia E. Molina
    • 1
  • Charles H. Lang
    • 1
  1. 1.Department of PhysiologyLouisiana State University Medical CenterNew OrleansUSA

Personalised recommendations