The Effects of Ethanol, Tumor Necrosis Factor, and Granulocyte Colony-Stimulating Factor on Lung Antibacterial Defenses

  • Steve Nelson
  • Gregory Bagby
  • Jeff Andresen
  • Chester Nakamura
  • Judd Shellito
  • Warren Summer
Part of the Advances in Experimental Medicine and Biology book series (AEMB, volume 288)


Respiratory tract infections are major causes of morbidity and mortality in individuals abusing alcohol (1). Sir William Osler, in his Principles and Practice of Medicine, stated that alcoholism was “perhaps the most potent predisposing factor” to bacterial pneumonia (2). Since this early observation, numerous other clinical investigations have reported evidence that alcoholics are at increased risk for severe pneumonia (3, 4). Despite recent technologic advances in the management of these infections and ever more “potent” antibiotics, there has been little decline in the mortality associated with this disease in alcohol consuming patients.


Host Defense Alveolar Macrophage Acute Alcohol Intoxication Bronchial Lavage Antibacterial Defense 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. 1.
    R. R. MacGregor, Alcohol and immune defense, JAMA 256:1474 (1986).PubMedCrossRefGoogle Scholar
  2. 2.
    W. Osler, “The principles and practice of medicine,” D. Appleton (1905).Google Scholar
  3. 3.
    J. P. Nolan, Alcohol as a factor in the illness of university service patients, Am. J. Med. Sci. 249:135 (1965).PubMedCrossRefGoogle Scholar
  4. 4.
    J. R. Tillotson and A. M. Lerner, Pneumonias caused by gram-negative bacilli, Medicine 45:65 (1966).PubMedCrossRefGoogle Scholar
  5. 5.
    W. G. Johanson, Prevention of respiratory tract infection, Am. J. Med. 76:69 (1984).PubMedCrossRefGoogle Scholar
  6. 6.
    G. M. Green, G. J. Jakab, R. B. Low, and G. S. Davis, Defense mechanisms of the respiratory membrane, Am. Rev. Respir. Dis. 115:479 (1977).PubMedGoogle Scholar
  7. 7.
    E. Goldstein, W. Lippert, and D. Warshauer, Pulmonary alveolar macrophage: defender against bacterial infection of the lung, J. Clin. Invest. 54:519 (1974).PubMedCrossRefGoogle Scholar
  8. 8.
    A. O. S. Fels and Z. A. Cohn, The alveolar macrophage, J. Appl. Physiol.60:353 (1986).PubMedGoogle Scholar
  9. 9.
    C. F. Nathan, Secretory products of macrophages, J. Clin. Invest. 79:319 (1987).PubMedCrossRefGoogle Scholar
  10. 10.
    C. A. Dinarello and J. W. Mier, Lymphokines, N. Engl. J. Med. 317:940 (1987).CrossRefGoogle Scholar
  11. 11.
    D. K. Blanchard, J. Y. Djeu, T. W. Klein, H. Friedman, and W. E. Stewart, II, Protective effects of tumor necrosis factor in experimental Legionella pneumophila infections of mice via activation of PMN function, J. Leuk. Biol. 43:429 (1988).Google Scholar
  12. 12.
    S. Nelson, G. J. Bagby, B. G. Bainton, L. A. Wilson, J. J. Thompson, and W. R. Summer, Compartmentalization of intraalveolar and systemic lipopoly-saccharide-induced tumor necrosis factor and the pulmonary inflammatory response, J. Infect. Dis. 159:189 (1989).PubMedCrossRefGoogle Scholar
  13. 13.
    S. Nelson, G. J. Bagby, and W. R. Summer, Alcohol-induced suppression of tumor necrosis factor: a potential risk factor for secondary infection in the acquired immunodeficiency syndrome, in: “Alcohol, Immunosuppression, and AIDS,” D. Seminara, R. Watson, and A. Pawlowski, eds., Alan R. Liss, Inc., NY (1989).Google Scholar
  14. 14.
    R. M. Strieter, D. G. Remick, J. P. Lynch, III, M. Genord, C. Raiford, R. Spengler, and S. L. Kunkel, Differential regulation of tumor necrosis factor-alpha in human alveolar macrophages and peripheral blood monocytes: a cellular and molecular analysis, Am. J. Respir. Cell. Mol. Biol. 1:57 (1989).PubMedGoogle Scholar
  15. 15.
    S. Nelson, P. Noel, R. Bokulic, G. J. Bagby, and W. R. Summer, Murine recombinant tumor necrosis factor enhances host defenses against Staphylococcus aureus (Abstract), Am. Rev. Respir. Dis. 139S:357 (1989).Google Scholar
  16. 16.
    B. Beutler, I. W. Milsark, and A. C. Cerami, Passive immunization against cachectin/tumor necrosis factor protects mice from lethal effect of endotoxin, Science 229:869 (1985).PubMedCrossRefGoogle Scholar
  17. 17.
    K. J. Tracey, Y. Fong, D. G. Hesse, K. R. Manogue, A. T. Lee, G. C. Kuo, S. F. Lowry, and A. Cerami, Anti-cachectin/TNF monoclonal antibodies prevent septic shock during lethal bacteremia, Nature 330:662 (1987).PubMedCrossRefGoogle Scholar
  18. 18.
    G. C. Okeson, and M. B. Divertie, Cilia and bronchial clearance: The effects of pharmacologic agents and disease, Mayo Clin. Proc. 45:361 (1970).PubMedGoogle Scholar
  19. 19.
    J. S. Bomalaski and J. P. Phair, Alcohol, immunosuppression, and the lung, Arch. Intern. Med. 142:2073 (1982).PubMedCrossRefGoogle Scholar
  20. 20.
    J. J. Guarneri and G. A. Laurenzi, Effect of alcohol on the mobilization of alveolar macrophages, J. Lab. Clin. Med. 72:40 (1968).PubMedGoogle Scholar
  21. 21.
    D. Rimland and W. L. Hand, The effect of ethanol on adherence and phagocytosis by rabbit alveolar macrophages, J. Lab. Clin. Med. 95:918 (1980).PubMedGoogle Scholar
  22. 22.
    D. Rimland, Mechanisms of ethanol-induced defects of alveolar macrophage function, Alcohol Clin. Exp. Res. 8:73 (1983).Google Scholar
  23. 23.
    D. B. Louria, Susceptibility to infection during experimental alcoholic intoxication, Trans. Assoc. Am. Physicians 76: 102 (1963).Google Scholar
  24. 24.
    C. L. Astry, G. A. Warr, and G. J. Jakab, Impairment of PMN immigration as a mechanism of alcohol-induced suppression of pulmonary antibacterial defenses, Am. Rev. Respir. Dis. 128:113 (1983).PubMedGoogle Scholar
  25. 25.
    R. R. MacGregor, M. Safford, and M. Shalit, Effect of ethanol on functions required for the delivery of neutrophils to sites of inflammation, J. Infect. D is. 157:682 (1988).CrossRefGoogle Scholar
  26. 26.
    J. R. Gamble, J. M. Harlan, S. J. Klebanoff, and M. A. Vadas, Stimulation of the adherence of neutrophils to umbilical vein endothelium by human recombinant tumor necrosis factor, Proc. Natl. Acad. Sci. 82:8667 (1985).PubMedCrossRefGoogle Scholar
  27. 27.
    K. J. Tracey, B. Beutler, S. F. Lowry, J. Merryweather, S. Wolpe, I. W. Milsark, R. J. Hariri, T. J. Fahey, A. Zentella, J. Albert, T. Shires, and A. Cerami, Shock and tissue injury induced by recombinant human cachectin, Science234:470 (1986).PubMedCrossRefGoogle Scholar
  28. 28.
    S. Nelson, G. J. Bagby, and W. R. Summer, Alcohol suppresses lipopolysaccharide-induced tumor necrosis factor activity in serum and lung, Life Sci44:673 (1989).PubMedCrossRefGoogle Scholar
  29. 29.
    S. Nelson, G. J. Bagby, B. G. Bainton, and W. R. Summer, The effects of acute and chronic alcoholism on tumor necrosis factor and the inflammatory response, J. Infect. Pis. 160:422 (1989).CrossRefGoogle Scholar
  30. 30.
    I. S. Figari and M. A. Palladino, Stimulation of neutrophil Chemotaxis by recombinant tumor necrosis factors alpha and beta (Abstract), Fed. Proc.46:562 (1987).Google Scholar
  31. 31.
    B. Averbook, T. Ulich, E. Jeffes, R. Yamamoto, G. Chow, I. Masunaka, and G. Granger, Human alpha lymphotoxin and TNF induce different types of inflammatory responses in normal tissue (Abstract), Fed. Proc. 46:562 (1987).Google Scholar
  32. 32.
    M. Yonemaru, H. Zheng, K. E. Stephens, A. Ishizaka, J. S. Sandhu, J. R. Hatherill, R. S. Hogue, and T. A. Raffin, Biphasic effect of tumor necrosis factor on polymorphonuclear leukocyte Chemotaxis (Abstract), Am. Rev. Respir. Pis. 137S:42 (1988).Google Scholar
  33. 33.
    N. B. D’Souza, G. J. Bagby, S. Nelson, C. H. Lang, and J. J. Spitzer, Acute alcohol infusion suppresses endotoxin-induced tumor necrosis factor production, Alcohol Clin. Exp. Res. 13:295 (1989).PubMedCrossRefGoogle Scholar
  34. 34.
    G. B. Toews, Peterminants of bacterial clearance from the lower respiratory tract, Sem. Resp. Infect. 1:68 (1986).Google Scholar
  35. 35.
    S. W. Chensue, D. G. Remick, C. Shmyr-Forsch, T. F. Beals, and S. L. Kunkel, Immunohistochemical demonstration of cytoplasmic and membrane-associated tumor necrosis factor in murine macrophages, Am. J. Pathol. 133:564 (1988).PubMedGoogle Scholar
  36. 36.
    E. Rubin and H. Rottenberg, Ethanol-induced injury and adaptation in biological membranes, Fed. Proc. 41:2465 (1982).PubMedGoogle Scholar
  37. 37.
    E. Girardin, G. E. Grau, J. M. Dayer, P. Roux-Lombard, the J5 Study Group, and P. H. Lambert, Tumor necrosis factor and interleukin-1 in the serum of children with severe infectious purpura, N. Engl. J. Med. 319:397 (1988).CrossRefGoogle Scholar
  38. 38.
    P. S. Imperia, G. Chikkappa, and P. G. Philips, Mechanism of inhibition of granulopoiesis by ethanol, Proc. Soc. Exp. Biol. Med. 175:219 (1984).PubMedGoogle Scholar
  39. 39.
    R. H. Weisbart, J. C. Gasson, and D. W. Golde, Colony-stimulating factors and host defense, Ann. Int. Med. 110:297 (1989).PubMedGoogle Scholar
  40. 40.
    H. P. Koeffler, J. Gasson, J. Ranyard, L. Souza, M. Shepard, and R. Munker, Recombinant human TNF alpha stimulates production of granulocyte colony-stimulating factor, Blood 70:55 (1987).PubMedGoogle Scholar

Copyright information

© Plenum Press, New York 1991

Authors and Affiliations

  • Steve Nelson
    • 1
  • Gregory Bagby
    • 1
  • Jeff Andresen
    • 2
  • Chester Nakamura
    • 1
  • Judd Shellito
    • 1
  • Warren Summer
    • 1
  1. 1.Departments of Medicine and PhysiologyLouisiana State University Medical CenterNew OrleansUSA
  2. 2.Amgen, Inc.Thousand OaksUSA

Personalised recommendations