Altered Cell-mediated Immunity and Increased Postoperative Infection Rate in Long-term Alcoholic Patients

Spies, Claudia; Dossow, Vera von; Eggers, Verena; Jetschmann, Gesine; El-Hilali, Ratiba; Egert, Julia; Fischer, Marc; Schröder, Torsten; Höflich, Conny; Sinha, Pranav; Paschen, Christian; Mirsalim, Parwis; Brunsch, Ralf; Hopf, Jürgen; Marks, Christian; Wernecke, Klaus‐D.; Pragst, F.; Ehrenreich, Hannelore; Müller, Christian; Tønnesen, Hanne; Oelkers, W.; Rohde, Wolfgang; Stein, Christoph; Kox, Wolfgang J.

doi:10.1097/00000542-200405000-00010

Cited by 119 publications

(102 citation statements)

References 70 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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“…The altered cytokine production results in a balance that favors an antiinfl ammatory profi le when exposed to surgical stress. 82 Cytokine abnormalities have been linked to the development of nosocomial sepsis in surgical and trauma patients.…”

Section: Surgical Patientsmentioning

confidence: 99%

“…64,65,82,[92][93][94][95] Two highly innovative studies suggested that the use of sedatives and opioids may infl uence the stress response and immune function. 48,49 Spies et al 48 demonstrated that the use of opioids may result in modulation of the stress response and result in improved outcomes.…”

Section: Management Of Sedationmentioning

confidence: 99%

Alcohol-Use Disorders in the Critically Ill Patient

Wit

Jones

Sessler

et al. 2010

Chest

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A lcohol-use disorders (AUDs) encompass a spectrum of disorders, including excessive use, abuse, dependence, and addiction. Abuse occurs when a patient experiences adverse socioeconomic or health consequences related to the use of the substance. 1 Dependence is present either when the patient experiences withdrawal symptoms on discontinuation of the substance or when larger amounts are necessary to achieve the desired effect. 1 Addiction is indicated by the patient experiencing a compulsive craving for a substance. 1 At any one time, a patient may have more than one of these disorders simultaneously present. The National Institutes of Health 2 have put forth guidelines that quantify excessive and unhealthy use of alcohol; a level of use above this threshold increases a patient's risk for health problems. 3 Men aged Յ 65 years who consume more than four standard drinks in a typical day or . 14 standard drinks in a typical week have excessive and unhealthy alcohol consumption. These volumes are halved for women of all ages and men aged .

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“…2 Furthermore, low interleukin-6/interleukin-10 (IL-6/IL-10) ratios have been associated with a significantly increased postoperative infection rate. 3 The immune response to tissue injury can be divided into innate and acquired responses.…”

Section: Spies M Kip a Lau Et Al Enhanced Hla-dr Expression Aftmentioning

confidence: 99%

Influence of Vaccination and Surgery on HLA-DR Expression in Patients with Upper Aerodigestive Tract Cancer

et al. 2008

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Altered Cell-mediated Immunity and Increased Postoperative Infection Rate in Long-term Alcoholic Patients

Cited by 119 publications

References 70 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

Alcohol-Use Disorders in the Critically Ill Patient

Influence of Vaccination and Surgery on HLA-DR Expression in Patients with Upper Aerodigestive Tract Cancer

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