Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Science and Society
  • Published:

Alcohol, host defence and society

Nature Reviews Immunology volume 2, pages 205–209 (2002)Cite this article

Abstract

Impaired health caused by alcohol abuse has been known throughout recorded history. Over the past century, alcohol abuse has been clearly linked to host susceptibility to infectious disease, particularly bacterial pneumonia. Recently, both acute and chronic alcohol intake have been shown to result in specific defects in innate and adaptive immunity; these could, in principle, be subjected to specific modulation to overcome the immunosuppressive effects of the most commonly abused substance in the Western world.

This is a preview of subscription content, access via your institution

Relevant articles

Open Access articles citing this article.

Access options

Buy this article

  • Purchase on Springer Link
  • Instant access to full article PDF
Buy now

Prices may be subject to local taxes which are calculated during checkout

Figure 1: Biphasic effect of alcohol consumption on mortality.
Figure 2: Overview of alcohol abuse and the immune system.

References

  1. World Health Organization Global Status Report on Alcohol. Management of Substance Dependence and Non-communicable Diseases. (World Health Organization, Geneva, Switzerland, 2001).

  2. Boffetta, P. & Garfinkel, L. Alcohol drinking and mortality among men enrolled in an American Cancer Society prospective study. Epidemiology 1, 342–348 (1990).

    Article  CAS  Google Scholar 

  3. Anderson, P. Alcohol consumption and all-cause mortality. Addiction 90, 481–484 (1995).

    Article  CAS  Google Scholar 

  4. Zureik, M. & Ducimetiere, P. High alcohol-related premature mortality in France: concordant estimates from a prospective cohort study and national mortality statistics. Alcohol Clin. Exp. Res. 20, 428–433 (1996).

    Article  CAS  Google Scholar 

  5. World Health Organization Alcohol and Health—Implications for Public Health Policy (Report of WHO working group, Oslo, 9–13 October 1995), (World Health Organization, Geneva, Switzerland, 1995).

  6. Leon, D. A. et al. Huge variation in Russian mortality rates 1984–94: artefact, alcohol, or what? Lancet 350, 383–388 (1997).

    Article  CAS  Google Scholar 

  7. Warren, K. R. et al. Fetal alcohol syndrome: an international perspective. Alcohol Clin. Exp. Res. 25, 202S–206S (2001).

    Article  CAS  Google Scholar 

  8. May, P. A. et al. Epidemiology of fetal alcohol syndrome in a South African community in the Western Cape Province. Am. J. Public Health 90, 1905–1912 (2000).

    Article  CAS  Google Scholar 

  9. Dufour, M. & Caces, F. Epidemiology of the medical consequences of alcohol. Alcohol Health Res. World 17, 265–271 (1993).

    Google Scholar 

  10. Gaziano, J. M. et al. Moderate alcohol intake, increased levels of high-density lipoprotein and its subfractions, and decreased risk of myocardial infarction. N. Engl. J. Med. 329, 1829–1834 (1993).

    Article  CAS  Google Scholar 

  11. Doll, R., Peto, R., Hall, E., Wheatley, K. & Gray, R. Mortality in relation to consumption of alcohol: 13 years' observations on male British doctors. BMJ 309, 911–918 (1994).

    Article  CAS  Google Scholar 

  12. Poikolainen, K. Alcohol and mortality: a review. J. Clin. Epidemiol. 48, 455–465 (1995).

    Article  CAS  Google Scholar 

  13. Lopez, A. D. & Murray, C. C. The global burden of disease, 1990–2020 Nature Med. 4, 1241–1243 (1998).

    Article  CAS  Google Scholar 

  14. Rush, B. An inquiry into the effects of ardent spirits upon the human body and mind. Q. J. Study Alcohol 4, 321–341 (1785).

    Google Scholar 

  15. Osler, W. M. The Principles and Practice of Medicine (Appleton & Lange, New York, 2001).

  16. Capps, J. A. & Coleman, G. H. Influence of alcohol on prognosis of pneumonia in Cook County Hospital. JAMA. 80, 750–752 (1923).

    Article  Google Scholar 

  17. Nolan, J. P. Alcohol as a factor in the illness of university service patients. Am. J. Med. Sci. 249, 135–142 (1965).

    Article  CAS  Google Scholar 

  18. Winterbauer, R. H., Bedon, G. A. & Ball, W. C. Jr. Recurrent pneumonia. Predisposing illness and clinical patterns in 158 patients. Ann. Int. Med. 70, 689–700 (1969).

    Article  CAS  Google Scholar 

  19. Fernandez-Sola, J. et al. High alcohol intake as a risk and prognostic factor for community-acquired pneumonia. Arch. Int. Med. 155, 1649–1654 (1995).

    Article  CAS  Google Scholar 

  20. Ruiz, M. et al. Etiology of community-acquired pneumonia: impact of age, comorbidity, and severity. Am. J. Respir. Crit. Care Med. 160, 397–405 (1999).

    Article  CAS  Google Scholar 

  21. Khan, K. N. & Yatsuhashi, H. Effect of alcohol consumption on the progression of hepatitis C virus infection and risk of hepatocellular carcinoma in Japanese patients. Alcohol Alcohol. 35, 286–295 (2000).

    Article  CAS  Google Scholar 

  22. Harris, D. R. et al. The relationship of acute transfusion-associated hepatitis to the development of cirrhosis in the presence of alcohol abuse. Ann Intern Med 134, 120–124 (2001).

    Article  CAS  Google Scholar 

  23. Lima, M. P., Pedro, R. J. & Rocha, M. D. Prevalence and risk factors for hepatitis C virus (HCV) infection among pregnant Brazilian women. Int. J. Gynaecol. Obstet. 70, 319–326 (2000).

    Article  CAS  Google Scholar 

  24. Moss, M., Bucher, B., Moore, F. A., Moore, E. E. & Parsons, P. E. The role of chronic alcohol abuse in the development of acute respiratory distress syndrome in adults. JAMA. 275, 50–54 (1996).

    Article  CAS  Google Scholar 

  25. Zisman, D. A. et al. Ethanol feeding impairs innate immunity and alters the expression of TH1- and TH2-phenotype cytokines in murine Klebsiella pneumonia. Alcohol Clin. Exp. Res. 22, 621–627 (1998).

    Article  CAS  Google Scholar 

  26. Hill, D. B., Devalaraja, R., Joshi-Barve, S., Barve, S. & McClain, C. J. Antioxidants attenuate nuclear factor-αB activation and tumor necrosis factor-α production in alcoholic hepatitis patient monocytes and rat Kupffer cells, in vitro. Clin. Biochem. 32, 563–570 (1999).

    Article  CAS  Google Scholar 

  27. Kishore, R., McMullen, M. R. & Nagy, L. E. Stabilization of tumor necrosis factor α mRNA by chronic ethanol. Role of A+U-rich elements and p38 mitogen-activated protein kinase signaling pathway. J. Biol. Chem. 276, 41930–41937 (2001).

    Article  CAS  Google Scholar 

  28. Zhang, Z. et al. Prolonged ethanol treatment enhances lipopolysaccharide/phorbol myristate acetate-induced tumor necrosis factor-α production in human monocytic cells. Alcohol Clin. Exp. Res. 25, 444–449 (2001).

    CAS  PubMed  Google Scholar 

  29. Reynolds, H. Y. Pulmonary host defenses. Alcohol Clin. Exp. Res. 19, 6–10 (1995).

    Article  CAS  Google Scholar 

  30. Nelson, S., Bagby, G. J., Bainton, B. G. & Summer, W. R. The effects of acute and chronic alcoholism on tumor necrosis factor and the inflammatory response. J. Infect. Dis. 160, 422–429 (1989).

    Article  CAS  Google Scholar 

  31. Kolls, J. K. et al. Differential effects of in vivo ethanol on LPS-induced TNF and nitric oxide production in the lung. Am J Physiol 268, L991–L998 (1995).

    CAS  PubMed  Google Scholar 

  32. Stoltz, D. A. et al. In vitro ethanol suppresses alveolar macrophage TNF-α during simian immunodeficiency virus infection. Am. J. Respir. Crit. Care Med. 161, 135–140 (2000).

    Article  CAS  Google Scholar 

  33. Szabo, G., Mandrekar, P. & Catalano, D. Inhibition of superantigen-induced T cell proliferation and monocyte IL-1β, TNF-α, and IL-6 production by acute ethanol treatment. J. Leukocyte Biol. 58, 342–350 (1995).

    Article  CAS  Google Scholar 

  34. Mandrekar, P., Catalano, D. & Szabo, G. Inhibition of lipopolysaccharide-mediated NFκB activation by ethanol in human monocytes. Int. Immunol. 11, 1781–1790 (1999).

    Article  CAS  Google Scholar 

  35. Boe, D. M., Nelson, S., Zhang, P. & Bagby, G. J. Acute ethanol intoxication suppresses lung chemokine production following infection with Streptococcus pneumoniae. J. Infect. Dis. 184, 1134–1142 (2001).

    Article  CAS  Google Scholar 

  36. Stoltz, D. A. et al. Ethanol suppression of the functional state of polymorphonuclear leukocytes obtained from uninfected and simian immunodeficiency virus infected rhesus macaques. Alcohol Clin. Exp. Res. 23, 878–884 (1999).

    Article  CAS  Google Scholar 

  37. Shellito, J. E. et al. Effect of alcohol consumption on host release of interleukin-17 during pulmonary infection with Klebsiella pneumoniae. Alcohol Clin. Exp. Res. 25, 872–881 (2001).

    Article  CAS  Google Scholar 

  38. Ye, P. et al. Requirement of interleukin 17 receptor signaling for lung CXC chemokine and granulocyte colony-stimulating factor expression, neutrophil recruitment, and host defense. J. Exp. Med. 194, 519–528 (2001).

    Article  CAS  Google Scholar 

  39. Brayton, R. G., Stokes, P. E., Schwartz, M. S. & Louria, D. B. Effect of alcohol and various diseases on leukocyte mobilization, phagocytosis and intracellular bacterial killing. N. Engl. J. Med. 282, 123–128 (1970).

    Article  CAS  Google Scholar 

  40. MacGregor, R. R., Gluckman, S. J. & Senior, J. R. Granulocyte function and levels of immunoglobulins and complement in patients admitted for withdrawal from alcohol. J. Infect. Dis. 138, 747–755 (1978).

    Article  CAS  Google Scholar 

  41. Xie, J., Kolls, J., Bagby, G. & Greenberg, S. S. Independent suppression of nitric oxide and TNFα in the lung of conscious rats by ethanol. FASEB J. 9, 253–261 (1995).

    Article  CAS  Google Scholar 

  42. Zhang, Z. et al. Inhibition of TNF-α processing and TACE-mediated ectodomain shedding by ethanol. J. Leukocyte Biol. 67, 856–862 (2000).

    Article  CAS  Google Scholar 

  43. Sibley, D. & Jerrells, T. R. Alcohol consumption by C57BL/6 mice is associated with depletion of lymphoid cells from the gut-associated lymphoid tissues and altered resistance to oral infections with Salmonella typhimurium. J. Infect. Dis. 182, 482–489 (2000).

    Article  CAS  Google Scholar 

  44. Shao, H., Zhou, J. & Ewald, S. J. Regulation of signal transduction and DNA fragmentation in thymocytes by ethanol. Cell. Immunol. 164, 11–19 (1995).

    Article  CAS  Google Scholar 

  45. Waltenbaugh, C. & Peterson, J. D. Ethanol impairs the induction of delayed hypersensitivity in C57BL/6 mice. Alcohol 14, 149–153 (1997).

    Article  CAS  Google Scholar 

  46. Messingham, K. A., Fontanilla, C. V., Colantoni, A., Duffner, L. A. & Kovacs, E. J. Cellular immunity after ethanol exposure and burn injury: dose and time dependence. Alcohol 22, 35–44 (2000).

    Article  CAS  Google Scholar 

  47. Saad, A. J., Domiati-Saad, R. & Jerrells, T. R. Ethanol ingestion increases susceptibility of mice to Listeria monocytogenes. Alcohol Clin. Exp. Res. 17, 75–85 (1993).

    Article  CAS  Google Scholar 

  48. Spitzer, J. H. & Meadows, G. G. Modulation of perforin, granzyme A, and granzyme B in murine natural killer (NK), IL2 stimulated NK, and lymphokine-activated killer cells by alcohol consumption. Cell Immunol. 194, 205–212 (1999).

    Article  CAS  Google Scholar 

  49. Lieber, C. S. Ethanol metabolism, cirrhosis and alcoholism. Clin. Chim. Acta 257, 59–84 (1997).

    Article  CAS  Google Scholar 

  50. Rolla, R. et al. Detection of circulating antibodies against malondialdehyde–acetaldehyde adducts in patients with alcohol-induced liver disease. Hepatology 31, 878–884 (2000).

    Article  CAS  Google Scholar 

  51. Thurman, R. G. et al. The role of gut-derived bacterial toxins and free radicals in alcohol-induced liver injury. J. Gastroenterol. Hepatol. 13 (Suppl.), S39–S50 (1998).

    Article  CAS  Google Scholar 

  52. Uesugi, T., Froh, M., Arteel, G. E., Bradford, B. U. & Thurman, R. G. Toll-like receptor 4 is involved in the mechanism of early alcohol-induced liver injury in mice. Hepatology 34, 101–108 (2001).

    Article  CAS  Google Scholar 

  53. Yin, M. et al. Essential role of tumor necrosis factor α in alcohol-induced liver injury in mice. Gastroenterology 117, 942–952 (1999).

    Article  CAS  Google Scholar 

  54. Hong, F., Nguyen, V. A. & Gao, B. Tumor necrosis factor α attenuates interferon α signaling in the liver: involvement of SOCS3 and SHP2 and implication in resistance to interferon therapy. FASEB J. 15, 1595–1597 (2001).

    Article  CAS  Google Scholar 

  55. Szabo, G., Mandrekar, P., Dolganiuc, A., Catalano, D. & Kodys, K. Reduced alloreactive T-cell activation after alcohol intake is due to impaired monocyte accessory cell function and correlates with elevated IL-10, IL-13, and decreased IFNγ levels. Alcohol Clin. Exp. Res. 25, 1766–1772 (2001).

    CAS  PubMed  Google Scholar 

  56. Reddy, R. C. et al. Alveolar macrophage deactivation in murine septic peritonitis: role of interleukin 10. Infect. Immun. 69, 1394–1401 (2001).

    Article  CAS  Google Scholar 

  57. Turecki, G., Rouleau, G. A. & Alda, M. Family density of alcoholism and linkage information in the analysis of the COGA data. Genet. Epidemiol. 17 (Suppl. 1), S361–S366 (1999).

    Article  Google Scholar 

  58. Peterson, L. E. et al. A genome-wide search for susceptibility genes linked to alcohol dependence. Genet. Epidemiol. 17 (Suppl. 1), S295–S300 (1999).

    Article  Google Scholar 

  59. Garver, E. et al. Eliciting the low-activity aldehyde dehydrogenase Asian phenotype by an antisense mechanism results in an aversion to ethanol. J. Exp. Med. 194, 571–580 (2001).

    Article  CAS  Google Scholar 

  60. Kolls, J. K. et al. Adenoviral-mediated interferon-γ gene therapy augments pulmonary host defense of ethanol-treated rats. Alcohol Clin. Exp. Res. 22, 157–162 (1998).

    Article  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. LSU Health Sciences Center Alcohol Research Center,

    Steve Nelson & Jay K. Kolls

  2. Section of Pulmonary Critical Care, LSU Health Sciences Center, 533 Bolivar Street, New Orleans, 70112, Louisiana, USA

    Steve Nelson & Jay K. Kolls

Authors
  1. Steve Nelson
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Jay K. Kolls
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Jay K. Kolls.

Related links

Related links

DATABASES

LocusLink

IκBα

IL-10

IL-17

interleukin-1β

liver mitochondrial aldehyde dehydrogenase 2

p55 TNF receptor

perforin

TACE

Toll-like receptor 4

TNF-α

 Emedicine

ARDS

alcohol psychosis

alcoholic polyneuropathy

bacterial pneumonia

chronic pancreatitis

cirrhosis

fetal alcohol syndrome

hepatitis C

oesophageal varices

FURTHER INFORMATION

Alcohol Education and Research Council

Educational Resources and Social Policy

Eurocare

Institute of Alcohol Studies

Louisiana State University Health Sciences Alcohol Research Center

National Institute on Alcohol Abuse and Alcoholism:

Thomas Jefferson University Alcohol Research Center

Glossary

ADULT RESPIRATORY DISTRESS SYNDROME

(ARDS). This disease is characterized by the acute onset of hypoxaemia, bilateral infiltrates on chest X-rays and no evidence of left ventricular heart failure. It can be precipitated by sepsis, pneumonia, surgery and/or trauma.

ALCOHOLIC LIVER DISEASE

A spectrum of entities including steatohepatitis, or lipid accumulation in the liver associated with ethanol abuse, alcoholic hepatitis, which is an acute inflammatory response in the liver associated with ethanol abuse, and cirrhosis.

BACTERIAL TRANSLOCATION

Transfer of bacteria or bacterial products from the lumen of the gastrointestinal tract to mesenteric lymph nodes and into the portal circulation.

CIRRHOSIS

Micro- or macronodular fibrosis in the liver, which can result from chronic alcohol abuse.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Nelson, S., Kolls, J. Alcohol, host defence and society. Nat Rev Immunol 2, 205–209 (2002). https://doi.org/10.1038/nri744

Download citation

  • Issue Date:

  • DOI: https://doi.org/10.1038/nri744

This article is cited by

Search

Advanced search

Quick links

Nature Briefing

Sign up for the Nature Briefing newsletter — what matters in science, free to your inbox daily.

Get the most important science stories of the day, free in your inbox. Sign up for Nature Briefing