Alcoholism, infection and altered host defenses: A review of clinical and experimental observations

Smith, Fredrica E.; Palmer, Darwin L.

doi:10.1016/0021-9681(76)90066-7

Cited by 154 publications

(30 citation statements)

References 87 publications

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“…Excessive alcohol consumption is known to have deleterious effects on the immune system (1)(2)(3)(4)(5). Chronic alcohol administration in experimental animal systems leads to a decrease in the absolute numbers of CD4 + T lymphocytes from the periphery and the spleen as well as a reduction in their immune function (6)(7)(8)(9)(10)(11)(12).…”

Section: Introductionmentioning

confidence: 99%

Ethanol inhibits methionine adenosyltransferase II activity and S-adenosylmethionine biosynthesis and enhances caspase-3-dependent cell death in T lymphocytes: relevance to alcohol-induced immunosuppression

Hote¹,

Sahoo²,

Jani³

et al. 2008

The Journal of Nutritional Biochemistry

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An important aspect in alcohol abuse associated immune suppression is the loss of T helper CD4 + lymphocytes leading to an impairment of multiple immune functions. Our work has shown that ethanol can sensitize CD4 + T lymphocytes to activation-induced, caspase-3 dependent cell death (AICD). It has been demonstrated that formation of S-adenosylmethionine (SAMe) catalyzed by methionine adenosyltransferase II (MAT II) is essential for CD4 + T cell activation and proliferation. Since ethanol is known to affect SAMe metabolism in hepatocytes, we investigated the effect of ethanol on MAT II activity/expression, SAMe biosynthesis and cell survival in CD4 + T lymphocytes. We demonstrate for the first time that ethanol at a physiologically relevant concentration (25mM) substantially decreased the enzymatic activity of MAT II in T lymphocytes. Ethanol was observed to decrease the transcription of MAT2A, which encodes the catalytic subunit of MAT II and is vital for MAT II activity and SAMe biosynthesis. Further, correspondent to its effect on MAT II, ethanol decreased intracellular SAMe levels and enhanced caspase-3 dependent AICD. Importantly, restoration of intracellular SAMe levels by exogenous SAMe supplementation considerably decreased both caspase-3 activity and apoptotic death in T lymphocytes. In conclusion, our data shows that MAT II and SAMe are critical molecular components essential for CD4 + T cell survival which are affected by ethanol leading to enhanced Address correspondence to: Shirish Barve PhD, Professor, Department of Medicine, Pharmacology and Toxicology, University of Louisville Medical Center, 511 S. Floyd, MDR Bldg., Rm#526, Louisville, KY 40202. Tel. 502 852 -5245; Fax. 502 562 -4271; shirish.barve@louisville.edu. Publisher's Disclaimer: This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final citable form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain. AICD. Furthermore, these studies provide a clinical paradigm for the development of the much needed therapy using SAMe supplementation in the treatment of immune dysfunction induced by alcohol abuse. HHS Public Access

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Section: Introductionmentioning

confidence: 99%

Ethanol inhibits methionine adenosyltransferase II activity and S-adenosylmethionine biosynthesis and enhances caspase-3-dependent cell death in T lymphocytes: relevance to alcohol-induced immunosuppression

Hote¹,

Sahoo²,

Jani³

et al. 2008

The Journal of Nutritional Biochemistry

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“…However, effective opsonization of pneumococci by either immunoglobulin M (IgM) or IgG requires host complement components, making complement essential for recovery from pneumococcal disease (reviewed in reference 6). Patients with complement system defects, therefore, are highly susceptible to pneumococcal infections (1,10,14,28). Complement's importance in host resistance to pneumococcal bacteremia was demonstrated in an experimental model in which cobra venom factor was used to induce severe complement depletion of guinea pigs.…”

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confidence: 99%

Pneumolysin-Induced Complement Depletion during Experimental Pneumococcal Bacteremia

2001

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To quantify complement depletion by pneumolysin during Streptococcus pneumoniae bacteremia, cirrhotic and control rats were infected intravenously with one of three isogenic mutant strains of S. pneumoniae expressing different forms of pneumolysin. Outcome measures included clearance of the organisms from the bloodstream, alterations in 50% serum hemolytic complement (CH 50 ) activity and complement C3 levels during infection, and serum opsonic capacity at 18 h postinfection. Cirrhotic rats had significantly lower CH 50 and C3 levels than control rats, both before and after infection. However, initial complement levels did not predict bacterial load after 18 h of infection. Changes in CH 50 and C3 levels over the 18-h period correlated with numbers of H؉C؉ but not H؉C؊ or PLY؊ organisms in the bloodstream at 18 h postinfection. The sera of cirrhotic rats infected with the H؉C؉ strain had significantly decreased levels of C3 and showed significantly lower opsonizing activity for S. pneumoniae than sera from H؉C؉-infected control rats. These studies suggest that under limiting concentrations of complement, the expression of pneumolysin by pneumococci has a significant, negative effect on serum complement levels and reduces serum opsonic activity.

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“…(33) When alcoholics inhale large amounts of oropharingeal secretions containing significant amounts of bacteria able to produce infectious diseases, we need to acknowledge and emphasize that the activity of anaerobic germs and fungi should be considered, being especially alert to the possibility of multi-microbial infections, and therefore we should direct specific treatment accordingly.…”

Section: Discussionmentioning

confidence: 99%

Oropharynx microbiota among alcoholics and non-alcoholics

Golin

Mimica²,

Mimica³

1998

Sao Paulo Med. J.

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CONTEXT: The oropharynx microbiota plays an important role in the origin of infections, especially among alcoholics whose airway defenses are impaired. OBJECTIVE: To compare the normal oropharingeal flora in heavy alcohol drinker and non-alcoholics. PATIENTS: 117 persons, 58 heavy alcohol drinkers and 59 non-alcoholics. SETTING: Santa Casa de São Paulo Emergency Service. DESIGN: A blind prospective study. MAIN OUTCOMES MEASURES: Prevalence of aerobic and anaerobic bacteria, and fungi. RESULTS: The study of the oropharynx microbiota among heavy alcohol drinkers demonstrated the presence of anaerobic microorganisms in 84.5% of them, including: Bacteroides sp, Prevotella melaninogenica, Fusobacterium sp, Veilonella sp, Peptostreptococcus sp, Propionibacterium sp, Bifidobacterium sp and Clostridium sp, versus 30.5% (p<0.005) of non-alcoholics. Candida sp was present in 34.5% of heavy alcohol drinkers and 5.1% of non-alcoholics (p<0.005). Enterobacteria predominated among heavy alcohol drinkers (25%) compared with non-alcoholics (5.5%) only in the age group 14 to 34 years (p<0.05). CONCLUSION: Based upon these results, it was possible to conclude that the knowledge of the oropharynx microbiota among heavy drinkers and non-alcoholics has an important predictive value concerning probable etiologic agents of lower airway infections. Infections caused by anaerobic microorganisms and fungi should be taken into consideration during the choice of empirical therapy for heavy alcohol drinkers.

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Alcoholism, infection and altered host defenses: A review of clinical and experimental observations

Cited by 154 publications

References 87 publications

Ethanol inhibits methionine adenosyltransferase II activity and S-adenosylmethionine biosynthesis and enhances caspase-3-dependent cell death in T lymphocytes: relevance to alcohol-induced immunosuppression

Ethanol inhibits methionine adenosyltransferase II activity and S-adenosylmethionine biosynthesis and enhances caspase-3-dependent cell death in T lymphocytes: relevance to alcohol-induced immunosuppression

Pneumolysin-Induced Complement Depletion during Experimental Pneumococcal Bacteremia

Oropharynx microbiota among alcoholics and non-alcoholics

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