Medicine and Health Sciences Commons^™

Another Armed Cd4(+) T Cell Ready To Battle Hepatocellular Carcinoma, Roniel Cabrera, Gyongyi Szabo

Gyongyi Szabo

No abstract provided.

Tubercular Pancreatic Abscess Presenting As Fever And Cystic Pancreatic Lesion With Endoscopic Management., Jonathan Fenkel, Maya Spodik, Bheema Singu, Anthony Infantolino, Sandeep Deshmukh, David Loren

Sandeep Deshmukh

Isolated pancreatic tuberculosis is a rare presentation of tubercular infection. There are few reported cases of pancreatic tuberculosis diagnosed by endoscopic ultrasound with fine-needle aspiration (EUS FNA), though EUS is often used in the evaluation of pancreatic cystic lesions. We present a case of a tubercular pancreatic abscess presenting as a cystic lesion in a patient with undiagnosed immunodeficiency. The abscess was aspirated by EUS FNA and treated with endoscopic drainage and anti-mycobacterial medications.

A Prospective Study Of The Rate Of Progression In Compensated, Histologically Advanced Chronic Hepatitis C, Jules Dienstag, Marc Ghany, Timothy Morgan, Adrian Di Bisceglie, Herbert Bonkovsky, Hae-Young Kim, Leonard Seeff, Gyongyi Szabo, Elizabeth Wright, Richard Sterling, Gregory Everson, Karen Lindsay, William Lee, Anna Lok, Chihiro Morishima, Anne Stoddard, James Everhart

Gyongyi Szabo

The incidence of liver disease progression among subjects with histologically advanced but compensated chronic hepatitis C is incomplete. The Hepatitis C Antiviral Long-term Treatment against Cirrhosis Trial was a randomized study of 3.5 years of maintenance peginterferon treatment on liver disease progression among patients who had not cleared virus on peginterferon and ribavirin therapy. Patients were followed subsequently off therapy. Because maintenance peginterferon treatment did not alter liver disease progression, we analyzed treated and control patients together. Among 1,050 subjects (60% advanced fibrosis, 40% cirrhosis), we determined the rate of progression to cirrhosis over 4 years and of clinical outcomes …

Factors That Determine The Development And Progression Of Gastroesophageal Varices In Patients With Chronic Hepatitis C, Robert Fontana, Arun Sanyal, Marc Ghany, William Lee, Andrea Reid, Deepa Naishadham, Gregory Everson, Jeffrey Kahn, Adrian Di Bisceglie, Gyongyi Szabo, Timothy Morgan, James Everhart

Gyongyi Szabo

BACKGROUND and AIMS: We aimed to identify the incidence and predictors of de novo gastroesophageal variceal formation and progression in a large cohort of patients with chronic hepatitis C and advanced fibrosis. METHODS: All participants in the Hepatitis C Antiviral Long-Term Treatment against Cirrhosis Trial were offered an endoscopy before treatment and again after 4 years. Patients with varices at baseline also had an endoscopy at 2 years. Baseline laboratory and clinical parameters were analyzed as predictors of de novo variceal formation and variceal progression. RESULTS: De novo varices developed in 157 of the 598 (26.2%) patients. Most of the …

Alcohol Exposure As A Risk Factor For Adverse Outcomes In Elective Surgery, Bharath Nath, Youfu Li, James Carroll, Gyongyi Szabo, Jennifer Tseng, Shimul Shah

Gyongyi Szabo

BACKGROUND AND AIMS: Alcohol consumption is a well-documented determinant of adverse perioperative outcome. We sought to determine the effect of active alcohol consumption following elective surgery. METHODS: We queried discharge records from the American College of Surgeons' National Surgical Quality Improvement Program (NSQIP, 2005-2007) for all elective adult admissions. The 7,631 (2.5%) patients with documented alcohol use (active alcohol use of at least two drinks per day within 2 weeks of surgery; ETOH use) underwent elective surgery; 301,994 (97.5%) patients denied ETOH use. Multivariate analysis was performed with adjustments for demographic and comorbid factors. Primary outcome measures included length of …

Intervention At The Level Of The Neuroendocrine-Immune Axis And Postoperative Pneumonia Rate In Long-Term Alcoholics, Claudia Spies, Verena Eggers, Gyongyi Szabo, Alexandra Lau, Vera Von Dossow, Helge Schoenfeld, Hilke Althoff, Katrin Hegenscheid, Birgit Bohm, Torsten Schroeder, Sebastian Pfeiffer, Sabine Ziemer, Christian Paschen, Martin Klein, Christian Marks, Peter Miller, Michael Sander, Klaus-D. Wernecke, Evelin Achterberg, Udo Kaisers, Hans-Dieter Volk

Gyongyi Szabo

RATIONALE: Postoperative pneumonia is three to four times more frequent in patients with alcohol use disorders followed by prolonged intensive care unit (ICU) stay. Long-term alcohol use leads to an altered perioperative hypothalamus-pituitary-adrenal (HPA) axis and immunity. OBJECTIVES: The aim of this study was to evaluate HPA intervention with low-dose ethanol, morphine, or ketoconazole on the neuroendocrine-immune axis and development of postoperative pneumonia in long-term alcoholic patients. METHODS: In this randomized, double-blind controlled study, 122 consecutive patients undergoing elective surgery for aerodigestive tract cancer were included. Long-term alcohol use was defined as consuming at least 60 g of ethanol daily …

Role Of Elevated Monocyte Transforming Growth Factor Beta (Tgf Beta) Production In Posttrauma Immunosuppression, Carol Miller-Graziano, Gyongyi Szabo, Katherine Griffey, Bela Mehta, Karen Kodys, Donna Catalano

Gyongyi Szabo

We previously reported that increased production of prostaglandin E2 by monocytes is a pivotal mechanism in posttrauma immunopathology. Here we characterize monocyte levels of transforming growth factor beta and examine the effects of elevated transforming growth factor beta on prostaglandin E2 release by patients' monocytes. Trauma patients' and normals' monocyte supernates (+/- stimulation with muramyl dipeptide) were acid treated and assayed for transforming growth factor beta using the mink lung-cell bioassay. Alternatively, human transforming growth factor beta was added to patients' and normals' monocytes and prostaglandin E2 production assayed. Significantly elevated transforming growth factor beta levels (median = 181.7 pmol/10(6) …

Effect Of Ethanol On Inflammatory Responses. Implications For Pancreatitis, Gyongyi Szabo, Pranoti Mandrekar, Shilpa Oak, Julia Mayerle

Gyongyi Szabo

BACKGROUND/AIMS: Alcohol use alters inflammatory cell responses. While alcohol has direct effects on pancreatic acinar cells, activation of inflammatory cells is a major component of the pathology of alcoholic pancreatitis.

METHODS: The effects of acute or chronic alcohol exposure were evaluated in human monocytes on the production of TNFalpha or IL-10 production, pro-inflammatory gene and nuclear factor-kappaB (NF-kappaB) activation.

RESULTS: Moderate, acute alcohol consumption or equivalent doses of alcohol in vitro had anti-inflammatory effects on monocyte activation via inhibition of pro-inflammatory genes and NF-kappaB activation, inhibition of TNFalpha production and augmentation of the anti-inflammatory cytokine, IL-10. In contrast, acute alcohol …

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 Ifngamma Levels, Gyongyi Szabo, Pranoti Mandrekar, Angela Dolganiuc, Donna Catalano, Karen Kodys

Gyongyi Szabo

BACKGROUND: Immunosuppression associated with chronic alcohol use is characterized by reduced antigen-specific T-cell response and impaired delayed type hypersensitivity. Increasing evidence suggests in chronic alcohol consumption models that reduced antigen-specific T-cell proliferation is due to insufficient accessory cell function. Accessory cell function, a critical step in recognition of viral antigens, is reduced in chronic hepatitis C. The severity of hepatitis C is increased by alcohol consumption. Thus, we investigated the effects of alcohol consumption on accessory cell activity of monocytes in supporting alloreactive T-cell proliferation. METHODS: Alloreactive T-cell proliferation was evaluated in a one-way mixed lymphocyte reaction (MLR). Mononuclear cells …

Acute Alcohol Activates Stat3, Ap-1, And Sp-1 Transcription Factors Via The Family Of Src Kinases To Promote Il-10 Production In Human Monocytes, Oxana Norkina, Angela Dolganiuc, Taryn Shapiro, Karen Kodys, Pranoti Mandrekar, Gyongyi Szabo

Gyongyi Szabo

Alcohol consumption is associated with an imbalance in pro- and anti-inflammatory cytokines and immunosuppression, partially as a result of enhanced IL-10 production. The mechanisms of IL-10 induction by alcohol remain poorly understood. We identified that increased IL-10 production in human monocytes after acute in vivo alcohol consumption or in vitro alcohol treatment was associated with increased STAT3 activation. Alcohol alone induced and in combination with LPS augmented STAT3 phosphorylation at tyrosine 705 (tyr705) and serine 727 (ser727) residues and increased STAT3 binding to DNA. Upstream, alcohol activated the Src kinases, as indicated by an increase in phosphorylated and a decrease …

Elevated Tumor Necrosis Factor Alpha Production Concomitant To Elevated Prostaglandin E2 Production By Trauma Patients' Monocytes, Thomas Takayama, Carol Miller-Graziano, Gyongyi Szabo

Gyongyi Szabo

The level of tumor necrosis factor alpha (TNF alpha), a monokine implicated in mediating septic shock, is elevated in the blood of some patients with sepsis. Monocytes from 11 trauma patients and 11 burn patients were suboptimally stimulated with interferon gamma and muramyl dipeptide, an analogue of bacterial wall products. The patients with sepsis showed significantly greater total TNF alpha levels (secreted in combination with cell-associated) 3 days before septic episodes, as compared with normal controls (32.38 to 2231.76 ng/10(6) monocytes per milliliter, median = 121.03 ng/10(6) monocytes per milliliter; normal control: 0.00 to 18.20 ng/10(6) monocytes per milliliter, median …

Regulation Of Human Monocyte Functions By Acute Ethanol Treatment: Decreased Tumor Necrosis Factor-Alpha, Interleukin-1 Beta And Elevated Interleukin-10, And Transforming Growth Factor-Beta Production, Gyongyi Szabo, Pranoti Mandrekar, Linda Girouard, Donna Catalano

Gyongyi Szabo

We and others have previously shown that even acute ethanol exposure has the capacity to modulate immune functions, particularly monocyte functions. Herein, we tested the hypothesis that acute ethanol treatment inhibits inflammatory, while increasing inhibitory cytokine production in human blood monocytes that, in turn, could contribute to the overall immune abnormalities seen after alcohol use. Our data show that in vitro treatment of blood monocytes with a physiologically relevant dose of alcohol (25 mM) results in significantly decreased induction of tumor necrosis factor-alpha (TNF alpha) and interleukin (IL)-1 beta by bacterial stimulation of either Gram-positive [staphylococcal enterotoxin B (SEB), 1 …

Monocytes, Alcohol Use, And Altered Immunity, Gyongyi Szabo

Gyongyi Szabo

The immunomodulatory capacity of acute, moderate alcohol consumption was investigated in this study in nonalcoholic volunteers after 2 ml of vodka/kg body weight of alcohol consumption. There was a significant, transient increase in interleukin-12 and interferon-gamma (IFNgamma) levels in whole blood samples collected 4 hr after alcohol consumption in response to an ex vivo bacterial challenge with lipopolysaccharide (p < 0.02). However, decreased IFNgamma levels were produced by mononuclear cells collected later after alcohol consumption (16 hr), suggesting that acute alcohol consumption has a biphasic effect on IFNgamma inducibility. Furthermore, isolated blood monocytes collected 16 hr after alcohol consumption showed significantly …

Mechanisms Of Altered Monocyte Prostaglandin E2 Production In Severely Injured Patients, Carol Miller-Graziano, Mitchell Fink, Jia-Yan Wu, Gyongyi Szabo, Karen Kodys

Gyongyi Szabo

Monocytes from immunosuppressed trauma (11 patients) and burn (12 patients) patients stimulated with muramyl dipeptide, a potent prostaglandin E2 (PGE2) secretagogue, showed twofold greater PGE2 production compared with normal controls or immunocompetent patients. Monocyte plasminogen activator production was markedly depressed and inversely correlated to patients' monocyte hyper PGE2 production. Levels of the PGE2-producing monocyte subset (selected as high-affinity Fc+ receptors) were progressively elevated after injury in immunosuppressed patients, reaching 65% to 80% of the total monocyte population (39% for normal controls). Although early T-suppressor (Ts) lymphocytes did not augment monocyte PGE2 secretion, Ts lymphocytes that appeared late (greater than 12 …

Acute Alcohol Consumption Attenuates Interleukin-8 (Il-8) And Monocyte Chemoattractant Peptide-1 (Mcp-1) Induction In Response To Ex Vivo Stimulation, Gyongyi Szabo, Sangeeta Chavan, Pranoti Mandrekar, Donna Catalano

Gyongyi Szabo

No abstract provided.

Acute Ethanol Consumption Synergizes With Trauma To Increase Monocyte Tumor Necrosis Factor Alpha Production Late Postinjury, Gyongyi Szabo, Pranoti Mandrekar, Bikash Verma, Ann Isaac, Donna Catalano

Gyongyi Szabo

The hypothesis that acute ethanol uptake plus trauma can synergize to increase immunosuppression was tested. We found that, unlike non-alcohol-exposed patients, patients with acute alcohol use prior to trauma have a transient decrease in monocyte tumor necrosis factor alpha (TNF alpha) production during the very early postinjury (0-3 days) period. However, TNF alpha production by these alcohol-exposed patients' monocytes (M0) became hyperelevated late postinjury (> 9 days). Consequently, these massively elevated M0 TNF alpha levels can contribute to posttrauma immunosuppression after acute alcohol use. We also demonstrate that normal monocyte activation with the superantigen, Staphylococcus enterotoxin B (SEB), results in …

Regulation Of Monocyte Interleukin-12 Production By Acute Alcohol: A Role For Inhibition By Interleukin-10, Linda Girouard, Pranoti Mandrekar, Donna Catalano, Gyongyi Szabo

Gyongyi Szabo

Acute ethanol treatment results in decreased antigen presentation capacity (Th1-type immunity) and elevated interleukin IL-10 (Th2 cytokine) production in human monocytes. Monocytes can contribute to both Th1 (IL-12) and Th2 (IL-10) immune responses via production of IL-12 and IL-10, respectively. Thus, we tested the hypothesis that acute alcohol treatment might affect Th1/Th2 immune balance by altering monocyte production of IL-12 and IL-10. Neither acute ethanol treatment alone (25 to 100 mM) nor its combination with a bacterial challenge Staphylococcal enterotoxin B (SEB) induced IL-12 production in isolated blood monocytes. In contrast, the same physiological alcohol concentrations increased monocyte IL-10 levels, …

Inhibition Of Antigen-Presenting Cell Functions By Alcohol: Implications For Hepatitis C Virus Infection, Gyongyi Szabo, Angela Dolganiuc, Pranoti Mandrekar, Bernadette White

Gyongyi Szabo

The mechanisms of alcohol-induced immunosuppression include defects in innate and adaptive immune responses. Monocytes and dendritic cells (DCs) link innate and adaptive immune responses as they recognize viral antigens and induce antigen-specific T-cell activation. We investigated the effects of alcohol on antigen-presenting cell functions. Acute alcohol consumption by healthy volunteers (vodka, 2 ml/kg) resulted in significantly reduced antigen-presenting cell function of monocyte-derived DCs. Reduced allostimulatory capacity of DCs treated with alcohol in vitro correlated with decreased co-stimulatory molecule (B7.1 and B7.2) expression, as well as with reduced interleukin (IL)-12 and increased IL-10 concentrations, in mixed lymphocyte cultures. Dendritic cells recognize …

Viral And Host Factors Induce Macrophage Activation And Loss Of Toll-Like Receptor Tolerance In Chronic Hcv Infection, Angela Dolganiuc, Oxana Norkina, Karen Kodys, Donna Catalano, Gennadiy Bakis, Christopher Marshall, Pranoti Mandrekar, Gyongyi Szabo

Gyongyi Szabo

BACKGROUND and AIMS: Persistent inflammation contributes to progression of liver damage in chronic HCV (cHCV) infection. Repeated exposure to toll-like receptor (TLR) ligands results in tolerance, a protective mechanism aimed at limiting inflammation.

METHODS: Monocytes/macrophages were repeatedly stimulated via proinflammatory cytokine-inducing TLRs and evaluated for activation markers.

RESULTS: Unlike monocytes of controls or patients with nonalcoholic steatohepatitis, the monocytes of cHCV patients were hyperresponsive and failed to show homo- or heterotolerance to TLR ligands, manifested by elevated tumor necrosis factor (TNF)-alpha production. Serum levels of interferon (IFN)-gamma, endotoxin (TLR4 ligand), and HCV core protein (TLR2 ligand) were elevated in cHCV …

Down-Regulation Of Tumor Necrosis Factor Alpha Activity By Acute Ethanol Treatment In Human Peripheral Blood Monocytes, Bikash Verma, Miklos Fogarasi, Gyongyi Szabo

Gyongyi Szabo

As the most commonly used drug that can modulate both metabolic and immune pathways, ethanol is evaluated in this report as a regulator of tumor necrosis factor alpha (TNF alpha) production in human peripheral blood monocytes (M phi) in combination with a variety of stimuli. While acute ethanol treatment did not induce TNF alpha in M phi, it was a potent down-regulator of M phi TNF alpha production whether induced by the combination of interferon-gamma plus muramyl dipeptide (MDP) (P < 0.001), lipopolysaccharide (LPS) alone (P < 0.01), or interferon-gamma plus LPS. Down-regulation of M phi TNF alpha by ethanol was dose dependent and statistically significant in the biologically relevant, 25-150 mM, ethanol concentration range. We also demonstrate that these ethanol concentrations did not affect M phi viability. TNF alpha down-regulation by ethanol was most effective when ethanol was administered 4 hr prior to MDP stimulation; however, it was also effective--though to a lesser extent--if it was added at the time of MDP stimulation. Furthermore, ethanol also down-regulated TNF alpha production of the in vivo preactivated M phi of trauma patients, which produce hyperelevated levels of TNF alpha. We have previously shown that the majority of posttrauma elevated M phi TNF alpha is produced by the M phi subpopulation expressing high-affinity type I Fc gamma receptors (Fc gamma RI). When the Fc gamma RI cross-linking-stimulated M phi subpopulation was treated with acute ethanol, TNF alpha production was suppressed again both in in vivo preactivated M phi of trauma patients and in M phi of normal controls.(ABSTRACT TRUNCATED AT 250 WORDS)

Acute Alcohol Consumption Inhibits Accessory Cell Function Of Monocytes And Dendritic Cells, Gyongyi Szabo, Donna Catalano, Bernadette White, Pranoti Mandrekar

Gyongyi Szabo

BACKGROUND: Alcohol affects both innate and acquired immune responses. Chronic alcoholics have reduced delayed-type hypersensitivity response and increased susceptibility to infections. In contrast, recent studies suggest that acute, moderate alcohol consumption has protective effects on mortality. Monocytes and dendritic cells (DC) play a central role in coordination of innate and adaptive immune responses and are pivotal in activation of T lymphocytes in an antigen-specific manner. In this study, we investigated the effects of acute, moderate alcohol consumption on antigen presenting cell function of blood monocytes and monocyte-derived myeloid dendritic cells. METHODS: Accessory cell function of human blood monocytes was tested …

Ethanol-Mediated Regulation Of Transcription Factors In Immunocompetent Cells, Gyongyi Szabo, Pranoti Mandrekar

Gyongyi Szabo

The immunomodulatory effects of acute and chronic alcohol use are characterized by impaired antigen-specific immune activation and by increased susceptibility to infections due to alterations in innate immune responses and inflammatory mediator production. The central feature of cellular responses to inflammatory and stress signals is the activation of the nuclear regulatory kappa B/Rel family of transcriptional factors via various surface receptor systems in immunocompetent cells. Activation of NF-kappa B, however, is regulated at multiple levels including I-kappa B degradation, nuclear translocation, and by interaction of NF-kappa B/Rel with other transcription factors. Data from our and other laboratories demonstrate that acute …

Elevated Monocyte Interleukin-6 (Il-6) Production In Immunosuppressed Trauma Patients. I. Role Of Fc Gamma Ri Cross-Linking Stimulation, Gyongyi Szabo, Karen Kodys, Carol Miller-Graziano

Gyongyi Szabo

This study demonstrates that immunodepressed trauma patients' monocytes produce elevated interleukin-6 to adherence, bacterial, and cytokine stimulation compared to immunocompetent trauma patients' or normals' monocytes, suggesting their in vivo preactivation possibly mediated by the hyperimmunoglobulinemia which characterizes these patients. Furthermore, stimulation of monocytes through cross-linking their Fc gamma RI induces and augments interleukin-6 (IL-6) production to subsequent stimulation both in trauma patients' (P less than 0.001) and in normals' (P less than 0.001) monocytes. As we reported earlier, immunodepressed trauma patients have an increased proportion of Fc gamma RI-bearing monocytes in their total monocyte population and here we show that …

The Critical Role Of Toll-Like Receptor (Tlr) 4 In Alcoholic Liver Disease Is Independent Of The Common Tlr Adapter Myd88, Istvan Hritz, Pranoti Mandrekar, Arumugam Velayudham, Donna Catalano, Angela Dolganiuc, Karen Kodys, Evelyn Kurt-Jones, Gyongyi Szabo

Gyongyi Szabo

The Toll-like receptor 4 (TLR4) that recognizes endotoxin, a trigger of inflammation in alcoholic liver disease (ALD), activates two signaling pathways utilizing different adapter molecules: the common TLR adapter, myeloid differentiation factor 88 (MyD88), or Toll/interleukin immune-response-domain-containing adaptor inducing interferon (IFN)-beta. The MyD88 pathway induces proinflammatory cytokine activation, a critical mediator of ALD. Here we evaluated the role of MyD88 in alcohol-induced liver injury in wild-type, TLR2-deficient, TLR4-deficient, or MyD88-deficient (knockout [KO]) mice after administration of the Lieber-De-Carli diet (4.5% volume/volume ethanol) or an isocaloric liquid control diet for 5 weeks. Alcohol feeding resulted in a significant increase in serum …

Additive Inhibition Of Dendritic Cell Allostimulatory Capacity By Alcohol And Hepatitis C Is Not Restored By Dc Maturation And Involves Abnormal Il-10 And Il-2 Induction, Angela Dolganiuc, Karen Kodys, Andrea Kopasz, Christopher Marshall, Pranoti Mandrekar, Gyongyi Szabo

Gyongyi Szabo

BACKGROUND: Excessive alcohol use results in impaired immunity, and it is associated with increased incidence and progression of chronic hepatitis C virus (HCV) infection. Here we investigated the effects of HCV infection and alcohol on myeloid dendritic cells (DC) that are critical in antiviral immunity.

METHODS: Immature and mature DCs were generated from monocytes of chronic HCV infected patients (HCV-DC) and controls (N-DC) with IL-4 plus granulocyte-macrophage colony stimulating factor (GM-CSF) in the presence or absence of alcohol (25 mM). DC allostimulatory capacity was tested in mixed lymphocyte reaction (MLR) and cytokine production by ELISA.

RESULTS: Allostimulatory capacity of HCV-DCs …

Moderate Alcohol Intake In Humans Attenuates Monocyte Inflammatory Responses: Inhibition Of Nuclear Regulatory Factor Kappa B And Induction Of Interleukin 10, Pranoti Mandrekar, Donna Catalano, Bernadette White, Gyongyi Szabo

Gyongyi Szabo

BACKGROUND: In contrast to the deleterious effects of chronic excessive alcohol consumption on the liver and cardiovascular system, modest alcohol intake, such as 1 to 2 drinks per day, has benefits on cardiovascular mortality. Little is known about the length of time or the amounts of alcohol consumed that may cause alterations in inflammatory cells such as monocytes that are crucial to atherosclerotic vascular disease. Here, we determine in vivo effects of acute alcohol consumption on inflammatory cytokine production and nuclear regulatory factor kappaB (NF-kappaB) binding in human monocytes. METHODS: Human blood monocytes were isolated by plastic adherence before and …

Acute Ethanol Treatment Modulates Toll-Like Receptor-4 Association With Lipid Rafts, Angela Dolganiuc, Genadyi Bakis, Karen Kodys, Pranoti Mandrekar, Gyongyi Szabo

Gyongyi Szabo

BACKGROUND: Alcohol, a substance that is most frequently abused, suppresses innate immune responses to microbial pathogens. The host senses pathogens via Toll-like receptors (TLRs). Recent studies indicate that alcohol affects TLR signaling. METHODS: Here, we hypothesized that acute alcohol treatment may interfere with early steps of membrane-associated TLR2 and TLR4 signaling at the level of lipid rafts. Human monocytes and Chinese hamster ovary (CHO) cells, transfected with human TLR2, TLR4, or CD14, were stimulated with peptidoglycan (PGN, TLR2 ligand) or lipopolysaccharide (LPS, TLR4 ligand) with or without alcohol (50 mM) and analyzed for cytokine production (enzyme-linked immunosorbent assay), nuclear factor-kappaB …