Life Sciences Commons^™

Aberrations In Post-Trauma Monocyte (Mo) Subpopulation: Role In Septic Shock Syndrome, Carol Miller-Graziano, Gyongyi Szabo, Karen Kodys, Katherine Griffey

Gyongyi Szabo

Appearance of increased proportions of monocytes bearing the 72kd(FcRI) receptor for IgG correlated to aberrant monocyte (MO) functions, depressed immune functions, and poor clinical outcome. The trauma patients' FcRI+ MO subpopulation produced the majority of their elevated IL-6, TNF alpha, TGF beta, and PGE2. IgG stimulation of patients' MO through FcRI not only stimulated TNF alpha, IL-6, and PGE2 levels, but also greatly augmented the levels of these monokines produced after subsequent bacterial challenge. Post-trauma increased IL-6 levels can lead to polyclonal B-cell activation and high levels of circulating, nonspecific IgG as seen in trauma patients. This nonspecific IgG triggers …

Critical Role Of Toll-Like Receptors And The Common Tlr Adaptor, Myd88, In Induction Of Granulomas And Liver Injury, Arumugam Velayudham, Istvan Hritz, Angela Dolganiuc, Pranoti Mandrekar, Evelyn Kurt-Jones, Gyongyi Szabo

Gyongyi Szabo

BACKGROUND/AIMS: Toll-like receptors (TLR) recognize pathogens and regulate innate immune activation. Here, we investigated the roles of TLR9 and the common TLR adaptor, MyD88, in liver injury.

METHODS: C57BL6, TLR9(-/-), IFNgamma(-/-) or MyD88(-/-) mice were primed with Propionibacterium acnes, TLR9 (CpG) or TLR2 (lipoteichoic acid) ligands followed by LPS challenge. ALT, cytokines and liver histology were assessed.

RESULTS: Selective priming through TLR9 but not TLR2 induced granulomas, elevated serum ALT, and sensitized C57BL6 mice to increased LPS-induced serum IL-6, IL-12 and IFNgamma levels. Further, TLR2 and TLR9 ligands synergized in induction of granulomas and sensitization to LPS-induced inflammation. IFNgamma induction …

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) …

Tacrolimus And Cyclosporine A Inhibit Allostimulatory Capacity And Cytokine Production Of Human Myeloid Dendritic Cells, Gyongyi Szabo, C. Gavala, Pranoti Mandrekar

Gyongyi Szabo

Myeloid dendritic cells (DCs) are pivotal in the recognition of alloantigens and, therefore, in the induction of allograft rejection. Induction of alloreactive T cell proliferation by myeloid DCs depends on the maturation of DCs, the expression of costimulatory molecules, and the cytokine environment. This study investigated the effects of tacrolimus and cyclosporine A (CsA) on DC maturation and allostimulatory capacity. Myeloid DCs were propagated from normal blood monocytes with interleukin (IL) 4 and GM-CSF for 7 days in the presence or absence of tacrolimus (FK506; 10 nM) or CsA (1 microg/mL). Exposure of DCs during maturation to tacrolimus or CsA …

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 …

Induction And Regulation Of Monocyte Procoagulant Activity, Gyongyi Szabo, Carol Miller-Graziano

Gyongyi Szabo

Monocyte (MO) procoagulant activity (PCA) is induced by various stimuli including allogeneic stimulation, immunocomplexes, and bacterial products. Antigen-antibody complex stimulation therefore represents a pathway for MO PCA induction. Activation of MO PCA has been demonstrated in immunocomplex disease and could represent a major pathology in transplanted immunocomplex disease patients. Stimulation of monocytes via their FcRI receptor has been demonstrated to induce TNF and PGE2. This report demonstrates that stimulation of the high-density FcRI receptor-bearing (FcRI+) MO by resetting with anti-Rh coated erythrocytes also induces significant PCA levels (P less than 0.001). Muramyl dipeptide (MDP), a Gram-positive bacterial cell wall analogue, …

The Opposite Effects Of Acute And Chronic Alcohol On Lipopolysaccharide-Induced Inflammation Are Linked To Irak-M In Human Monocytes, Pranoti Mandrekar, Shashi Bala, Donna Catalano, Karen Kodys, Gyongyi Szabo

Gyongyi Szabo

Impaired host defense after alcohol use is linked to altered cytokine production, however, acute and chronic alcohol differently modulate monocyte/macrophage activation. We hypothesized that in human monocytes, acute alcohol induces hyporesponsiveness to LPS, resulting in decreased TNF-alpha, whereas chronic alcohol increases TNF-alpha by sensitization to LPS. We found that acute alcohol increased IL-1R-associated kinase-monocyte (IRAK-M), a negative regulator of IRAK-1, in human monocytes. This was associated with decreased IkappaB alpha kinase activity, NFkappaB DNA binding, and NFkappaB-driven reporter activity after LPS stimulation. In contrast, chronic alcohol decreased IRAK-M expression but increased IRAK-1 and IKK kinase activities, NFkappaB DNA binding, and …

Innate Immune Response And Hepatic Inflammation, Gyongyi Szabo, Pranoti Mandrekar, Angela Dolganiuc

Gyongyi Szabo

Inflammation is a pathogenic component of various types of acute and chronic liver diseases, and it contributes to progressive liver damage and fibrosis. Cells of the innate immune system initiate and maintain hepatic inflammation though mediator production as a result of their activation by pathogen-derived products recognized by pattern recognition receptors. Innate immune cells, particularly dendritic cells, have a pivotal role in sensing pathogens and initiating adaptive immune responses by activation and regulation of T-lymphocyte responses. Although the liver provides a "tolerogenic" immune environment for antigen-specific T-cells, activation of Kupffer cells, recruited macrophages, and inflammatory cells results in production of …

Bone Marrow-Derived Immune Cells Mediate Sensitization To Liver Injury In A Myeloid Differentiation Factor 88-Dependent Fashion, Istvan Hritz, Arumugam Velayudham, Angela Dolganiuc, Karen Kodys, Pranoti Mandrekar, Evelyn Kurt-Jones, Gyongyi Szabo

Gyongyi Szabo

Toll-like receptors (TLRs) expressed on both immune cells and hepatocytes recognize microbial danger signals and regulate immune responses. Previous studies showed that TLR9 and TLR2 mediate Propionibacterium acnes-induced sensitization to lipopolysaccharide-triggered acute liver injury in mice. Ligand-specific activation of TLR2 and TLR9 are dependent on the common TLR adaptor, myeloid differentiation factor 88 (MyD88). Here, we dissected the role of MyD88 in parenchymal and bone marrow (BM)-derived cells in liver sensitization. Using chimeric mice with green fluorescent protein-expressing BM cells, we identified that P. acnes-induced liver inflammatory foci are of BM origin. Chimeras with MyD88-deficient BM showed no inflammatory foci …

Acute Ethanol Treatment Augments Interleukin-12 Production In Activated Human Monocytes, Gyongyi Szabo, Linda Girouard, Pranoti Mandrekar, Donna Catalano

Gyongyi Szabo

No abstract provided.

Myeloid Dendritic Cells Of Patients With Chronic Hcv Infection Induce Proliferation Of Regulatory T Lymphocytes, Angela Dolganiuc, Edward Paek, Karen Kodys, Joanne Thomas, Gyongyi Szabo

Gyongyi Szabo

BACKGROUND and AIMS: Dendritic cells (DCs) initiate and sustain an efficient T-lymphocyte response. Chronic hepatitis C virus (HCV) infection is associated with inefficient T-cell functions that fail to eradicate the virus, so defects in DC function might be involved in HCV pathogenesis. This study analyzed the activities of myeloid DCs and distinct CD4(+) T-cell populations in samples collected from patients with HCV. METHODS: The abilities of primary BDCA1(+) or monocyte-derived DCs from HCV patients (HCV-DC) to stimulate CD4(+), CD4(+)CD25(-), or different ratios of CD4(+)CD25(+)/CD4(+)CD25(-) T cells were evaluated in mixed lymphocyte reactions. T-cell proliferation and phenotype were evaluated by flow …

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 …

Altered Innate Immunity In Chronic Hepatitis C Infection: Cause Or Effect, Gyongyi Szabo, Serena Chang, Angela Dolganiuc

Gyongyi Szabo

No abstract provided.

Signalling Pathways In Alcohol-Induced Liver Inflammation, Pranoti Mandrekar, Gyongyi Szabo

Gyongyi Szabo

The pathogenesis of alcoholic liver injury involves interactions of several intracellular signalling pathways in different cell types of the liver. Alcohol-induced sensitization of liver macrophages to portal endotoxin/lipopolysaccharide (LPS) is considered a hallmark of alcoholic liver disease (ALD). Intracellular mechanisms associated with LPS-induced signalling play a crucial role in the initiation and progression of alcoholic liver injury, and are being extensively explored. LPS recognition by Toll-like receptor 4 (TLR4) on macrophages and other cell types in the liver, activation of downstream signalling pathways culminating in activation of transcription factors such as NFkappaB, AP-1 leads to increased inflammatory cytokine production in …

Increased Lipopolysaccharide Sensitivity In Alcoholic Fatty Livers Is Independent Of Leptin Deficiency And Toll-Like Receptor 4 (Tlr4) Or Tlr2 Mrna Expression, Laszlo Romics, Pranoti Mandrekar, Karen Kodys, Arumugam Velayudham, Yvonne Drechsler, Angela Dolganiuc, Gyongyi Szabo

Gyongyi Szabo

BACKGROUND: Both alcoholic (AFL) and nonalcoholic (NAFL) fatty livers show increased sensitivity to endotoxin-induced injury. Lipopolysaccharide (LPS) is recognized by toll-like receptor 4 (TLR4), whereas lipopeptide triggers TLR2 to induce common downstream activation of nuclear factor (NF)-kappaB and pro-inflammatory pathways that are activated in AFL and NAFL. METHODS: Serum alanine aminotransferase (ALT), tumor necrosis factor (TNF)-alpha, and interleukin (IL)-6 levels; hepatic NF-kappaB activity; and expression of TLR2, TLR4, inducible nitric oxide synthase (iNOS), and heme oxygenase (HO)-1 mRNAs were investigated in lean and leptin-deficient ob/ob mice after LPS challenge in combination with acute or chronic alcohol feeding. RESULTS: Increased LPS …

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 …

Inhibitory Effect Of Monocyte Reactive Antibodies On Monocyte Chemotaxis In Systemic Lupus Erythematosus, Gyula Szegedi, Katalin Lukacs, E. Bodolay, L. Gulacsi, Ildiko Sonkoly, Gyongyi Szabo, J. Szollosi

Gyongyi Szabo

Presence of different types of autoantibodies is a basic feature of systemic lupus erythematosus (SLE). Though monocytes, macrophages play an important role in cellular immunity, autoantibodies against monocytes have not been sufficiently studied. The authors used automatic fluorochromatic assay to detect monocyte reactive autoantibodies in the sera of SLE patients. Of SLE 35.5% sera showed complement-mediated monocytotoxic activity against healthy monocytes. Monocyte reactive SLE sera as well as monoclonal antibodies against human monocytes inhibited chemotaxis of control monocytes. The results suggest that monocyte reactive autoantibodies may play a role in the decreased monocyte number and defective monocyte functions observed in …

Selective Priming To Toll-Like Receptor 4 (Tlr4), Not Tlr2, Ligands By P. Acnes Involves Up-Regulation Of Md-2 In Mice, Laszlo Romics, Angela Dolganiuc, Karen Kodys, Yvonne Drechsler, Shilpa Oak, Arumugam Velayudham, Pranoti Mandrekar, Gyongyi Szabo

Gyongyi Szabo

Lipopolysaccharide (LPS) triggers cytokine production through Toll-like receptor 4 (TLR4), which shares downstream signaling pathways with TLR2. We investigated the roles of TLR2 and TLR4 in Propionibacterium acnes (P. acnes)-primed, LPS-induced liver damage using selective TLR ligands. Stock LPS induced interleukin 8 in both TLR4- and TLR2-expressing human embryonic kidney (HEK) 293 cells. Purified LPS (TLR4 ligand) activated HEK/TLR4 cells, while peptidoglycan and lipoteichoic acid (TLR2 ligands) activated HEK/TLR2 cells, respectively. In mice, P. acnes priming resulted in increased liver messenger RNA (mRNA) and serum levels of tumor necrosis factor alpha, interleukin 12, and interferon gamma (IFN-gamma) by both stock …

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 …

Human Monocytes, Macrophages, And Dendritic Cells: Alcohol Treatment Methods, Gyongyi Szabo, Pranoti Mandrekar

Gyongyi Szabo

Both acute and chronic alcohol consumption have significant immunomodulatory effects of which alterations in innate immune functions contribute to impaired antimicrobial defense and inflammatory responses. Blood monocytes, macrophages, and dendritic cells play a central role in innate immune recognition as these cells recognize pathogens, respond with inflammatory cytokine production, and induce antigen-specific T-lymphocyte activation. All of these innate immune cell functions are affected in humans by alcohol intake. Here, we summarize the different effects of acute and chronic alcohol on monocyte, macrophage, and dendritic cell functions in humans and describe methods for separation and functional evaluation of these cell types.

Antigen-Presenting Cells Under The Influence Of Alcohol, Audrey Lau, Gyongyi Szabo, Angus Thomson

Gyongyi Szabo

The negative influence of alcohol (ethanol) and its metabolites on innate and adaptive immunity is well-recognized. Much attention has recently been focused on the impact of acute and chronic alcohol exposure on antigen-presenting cells (APC). In particular, insights have been gained into how the properties of human blood monocytes and rodent macrophages are influenced by alcohol in vitro and in vivo. Here, we review the impact of alcohol on various aspects of APC function and the underlying mechanisms, including its effects on intracellular signaling events. We also discuss new information regarding the influence of alcohol on various APC populations in …

Alcohol-Induced Modulation Of Signaling Pathways In Liver Parenchymal And Nonparenchymal Cells: Implications For Immunity, Bharath Nath, Gyongyi Szabo

Gyongyi Szabo

Alcoholic liver injury involves a complex array of derangements in cellular signaling of hepatic parenchymal and nonparenchymal cells as well as cells of the immune system. In the hepatocyte, chronic ethanol abuse leads to lipid accumulation and liver steatosis. Multiple pathways are affected to promote lipid accumulation in the ethanol-exposed hepatocyte. Chronic ethanol renders Kupffer cells hyperresponsive to endotoxin, which results in production of inflammatory cytokines and the tumor necrosis factor-alpha via a toll-like receptor 4 dependent pathway, leading to inflammation and hepatic necrosis. Dysfunction of the innate and adaptive immune responses caused by ethanol contributes to impaired antiviral response, …

Polymorphonuclear Functions In Patients With Mixed Connective Tissue Disease, E. Bodolay, Katalin Lukacs, G. Frendl, Gyongyi Szabo, G. Arato, Gyula Szegedi

Gyongyi Szabo

Polymorphonuclear leukocytes (PMNs) from 29 patients with mixed connective tissue disease (MCTD) were studied "in vitro" for their phagocytic and chemotactic function as well as for granulocyte alkaline phosphatase (GAP) activity. Fc-receptor expression detected by EA-rosette formation was comparable to the control. Yeast-phagocytosis, C3b-receptor mediated phagocytosis and chemotaxis of PMNs, however, significantly decreased in MCTD. At the same time, photometric measure of alkaline phosphatase activity indicated a nearly two fold increase in PMNs from patients with MCTD. Although no correlation was found between PMN functions and the activity of the disease, PMN disorders may play a role in pathogenesis of …

Acute Alcohol Inhibits The Induction Of Nuclear Regulatory Factor Kappa B Activation Through Cd14/Toll-Like Receptor 4, Interleukin-1, And Tumor Necrosis Factor Receptors: A Common Mechanism Independent Of Inhibitory Kappa B Alpha Degradation, Pranoti Mandrekar, Angela Dolganiuc, Gary Bellerose, Karen Kodys, Laszlo Romics, Rabia Nizamani, Gyongyi Szabo

Gyongyi Szabo

BACKGROUND: Nuclear translocation and DNA binding of the nuclear factor kappaB (NF-kappaB) is an early event in inflammatory cell activation in response to stimulation with bacterial components or cytokines. Cell activation via different receptors culminates in a common pathway leading to NF-kappaB activation and proinflammatory cytokine induction. We have previously shown that acute alcohol inhibits NF-kappaB activation by lipopolysaccharide (LPS) in human monocytes. Here we investigated whether acute alcohol treatment of human monocytes also inhibits NF-kappaB when induced through activation of the interleukin (IL)-1 or tumor necrosis factor (TNF) receptors. METHODS: Human peripheral blood monocytes were treated with LPS, TNFalpha, …

Monocyte Functions In Patients With Mixed Connective Tissue Disease, E. Bodolay, Katalin Lukacs, Gyongyi Szabo, G. Frendl, T. Ben, Gyula Szegedi

Gyongyi Szabo

The authors investigated the number and functions of peripheral blood monocytes in patients with mixed connective tissue disease. Moderate monocytopenia was detected in the active stage of the disease. There was a close correlation between the sensitized sheep red blood cell binding capacity of monocytes and the elevated levels of circulating immune complexes. The yeast phagocytosis of monocytes and the chemotactic activity were normal in patients with mixed connective tissue disease. C3b receptor mediated phagocytosis of monocytes decreased in the active and inactive stages of the disease. This study suggests that the decreased function of C3b receptors of monocytes is …

Human Macrophages Degrade Tryptophan Upon Induction By Interferon-Gamma, Ernst Werner, Gabriele Bitterlich, Dietmar Fuchs, Arno Hausen, Gilbert Reibnegger, Gyongyi Szabo, Manfred Dierich, Helmut Wachter

Gyongyi Szabo

Human peripheral blood mononuclear cells, monocytes-macrophages and T-cells were stimulated with human recombinant interferon-gamma, interferon-alpha and phytohemagglutinin. The culture supernatants were analyzed for tryptophan, kynurenine, 3-hydroxyanthranilic acid, anthranilic acid and neopterin by high performance liquid chromatography. Tryptophan was decreased and the four other compounds were increased in supernatants of peripheral blood mononuclear cells activated by interferon-gamma (250 U/ml), interferon-alpha (10.000 U/ml) and phytohemagglutinin (1 microgram/ml). After splitting of peripheral blood mononuclear cells by adherence, the monocytes and macrophages but not the T-cells degraded tryptophan upon stimulation by interferon-gamma in a dose dependent manner. Supernatants of phytohemagglutinin stimulated but not of …

New Insights Into The The Molecular Mechanisms Of Alcoholic Hepatitis: A Potential Role For Nf-Kappab Activation, Gyongyi Szabo

Gyongyi Szabo

No abstract provided.

Vsl#3 Probiotic Treatment Attenuates Fibrosis Without Changes In Steatohepatitis In A Diet-Induced Nonalcoholic Steatohepatitis Model In Mice, Arumugam Velayudham, Angela Dolganiuc, Michael Ellis, Jan Petrasek, Karen Kodys, Pranoti Mandrekar, Gyongyi Szabo

Gyongyi Szabo

Nonalcoholic fatty liver disease (NAFLD) and its advanced stage, nonalcoholic steatohepatitis (NASH), are the most common causes of chronic liver disease in the United States. NASH features the metabolic syndrome, inflammation, and fibrosis. Probiotics exhibit immunoregulatory and anti-inflammatory activity. We tested the hypothesis that probiotic VSL#3 may ameliorate the methionine-choline-deficient (MCD) diet-induced mouse model of NASH. MCD diet resulted in NASH in C57BL/6 mice compared to methionine-choline-supplemented (MCS) diet feeding evidenced by liver steatosis, increased triglycerides, inflammatory cell accumulation, increased tumor necrosis factor alpha levels, and fibrosis. VSL#3 failed to prevent MCD-induced liver steatosis or inflammation. MCD diet, even 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, …