Alcohol Infection Research Articles

Pemeriksaan Ultrasonografi Hepar menjadi Pemeriksaan Penunjang yang Tepat untuk Diagnosa Hepatitis

Hepatitis is inflammation of the liver due to viral or alcohol infection. Hepatitis can cause death and the case always increases every year both in Indonesia and the world. The aim of this study is to describe and evaluate the management of examination such as patient preparation procedure, tool preparation, patient position, transducer placement, transducer used, and ultrasound image of hepatitis. This research was conducted by qualitative descriptive method. The population is all patients who perform liver ultrasound examination at RSUD Cengkareng Jakarta. The samples used were patients who performed liver ultrasound examination with clinical hepatitis. The number of samples used is 2 patients. After being analyzed and observed, ultrasonography is an accurate and accurate examination of the hepatitis case. Additional scripting techniques are sometimes required in certain cases to make the results more optimal. Based on this research, it can be expected that ultrasound modalities can be used as an appropriate supporting tool in establishing clinical hepatitis with accurate, fast, cheap and safe results.

The involvement of GM-CSF deficiencies in parallel pathways of pulmonary alveolar proteinosis and the alcoholic lung.

Chronic alcohol consumption renders the lung more susceptible to infections by disrupting essential alveolar macrophage functions. Emerging evidence suggests that these functional deficits are due, in part, to a suppression of GM-CSF signaling, which is believed to compromise monocyte growth and maturation in the lung. However, in addition to controlling monocyte behaviors, GM-CSF also regulates surfactant homeostasis. For example, mice with targeted deletion of the gene for GM-CSF accumulate large amounts of surfactant phospholipids in their lungs. Moreover, decreased GM-CSF signaling in humans has been linked to the development of pulmonary alveolar proteinosis (PAP), a rare disorder in which surfactant lipids and proteins accumulate in alveolar macrophages and the lung exhibits enhanced susceptibility to infection. Consistent with parallel mechanisms in the PAP and alcoholic lung, we have recently reported that levels of intrapulmonary lipids, specifically triglycerides and free fatty acids, are increased in BAL fluid, whole lung digests and alveolar macrophages of chronically alcohol exposed rats. Additionally, we showed that uptake of saturated fatty acids alone could induce phenotypic and functional changes in alveolar macrophages that mimicked those in the alcohol-exposed rat and human lung. Herein, we discuss the role of GM-CSF in surfactant homeostasis and highlight the evidence that links decreased GM-CSF signaling to alveolar macrophage dysfunction in both the PAP and alcohol-exposed lung. Moreover, we discuss how lipid accumulation itself might contribute to altering alveolar macrophage function and propose how targeting these mechanisms could be employed for reducing the susceptibility to pulmonary infections in alcoholics.

Effect of glycyrrhizin on the intratracheal infection of Klebsiella pneumoniae in NOD/scid IL-2Rγnull mice inoculated with alcoholic patient white blood cells (IRC4P.609)

Abstract Humanized mice created with alcoholic patient white blood cells (patient chimeras) are extremely susceptible to infection with K. pneumoniae. M2Mϕ in patient WBC are responsible for impairing the host antibacterial response of the chimeras. Since glycyrrhizin is known as an inhibitor of M2Mϕ activities, in this study, the effect of glycyrrhizin on K. pneumoniae infection in these chimeras was investigated. Patient chimeras (γ-irradiated-NOD/scid IL-2Rγnull mice inoculated 5 x 106 cells/mouse of alcoholic patient WBC) were infected intratracheally with 100 CFU/mouse of K. pneumoniae, and treated with 10 mg/kg of glycyrrhizin (48 hours before and 2 h after infection, Minophargen Pharmaceutical Co., Ltd., Tokyo, Japan). In the results, severe bacterial growth was demonstrated in the liver (2.7 x 107 CFU/g organ), kidney (2.9 x 107 CFU/g organ), and spleen (1.4 x 109 CFU/g organ) of patient chimeras 24 h after the infection. Contrarily, only 0.15 - 6 x 104 CFU/g organ of the pathogen were detected in these organs of patient chimeras treated with glycyrrhizin. Similarly, bacterial growth was minimal in the organs of healthy chimeras (γ-irradiated-NOD/scid IL-2Rγnull mice inoculated with healthy donor WBC). These results suggest that K. pneumoniae infections in alcoholics may be controllable by glycyrrhizin, an inhibitor of M2Mϕ activities.

M2b Macrophage Elimination and Improved Resistance of Mice with Chronic Alcohol Consumption to Opportunistic Infections

Alcohol abuse was found to predispose persons to opportunistic infections. In this study, we tried to improve the host antibacterial resistance of chronic alcohol-consuming (CAC) mice to opportunistic infections. Bactericidal macrophages with functions to produce IL-12 and to express mRNAs for CXCL9 and inducible nitric oxide synthase (M1 macrophages) were characterized as the main effector cells in host antibacterial innate immunities against infections with opportunistic pathogens. However, CAC mice were found to be carriers of M2b macrophages [macrophages with functions to produce IL-10 and to express mRNAs for CD163, chemokine ligand (CCL)1, and LIGHT (homologous to lymphotoxin, exhibits inducible expression, competes with herpes simplex virus glycoprotein D for high-voltage electron microscopy on T cells)], which were inhibitory on macrophage conversion from resident macrophages to M1 macrophages. Under treatment with CCL1 antisense oligodeoxynucleotides, a specific inhibitor of M2b macrophages, CAC mouse macrophages reverted to resident macrophages, and M1 macrophages were induced by a bacterial antigen from macrophages of CAC mice that were previously treated with the oligodeoxynucleotides. Opportunistic infections (enterococcal translocation and Klebsiella pneumonia) in CAC mice were completely controlled by CCL1 antisense oligodeoxynucleotides. These results indicate that certain opportunistic infections in alcoholics are controllable through the modulation of M2b macrophages.

Chronic ethanol exposure selectively inhibits the influenza-specific CD8 T cell response during influenza a virus infection.

It is well established that chronic ethanol (EtOH) consumption is associated with increased incidence and disease severity of respiratory infections. Our recent work demonstrates this increase in disease severity to influenza A virus (IAV) infections is due, in part, to a failure to mount a robust IAV-specific CD8 T cell response along with a specific impairment in the ability of these T cells to produce interferon γ (IFNγ). However, the full extent of the lesion in the effector CD8 T cell compartment during chronic EtOH consumption remains unknown. Utilizing the Meadows-Cook murine model of chronic alcohol consumption, mice received EtOH in their drinking water for 8 or 12 weeks. Mice were challenged intranasally with IAV, and the activation and effector functions of IAV-specific CD8 T cells were determined in both the lung-draining lymph nodes (dLN) and lungs. Our results confirm the defect in IFNγ production; however, the ability of IAV-specific T cells to produce tumor necrosis factor α (TNFα) and interleukin-2 (IL-2) in EtOH-consuming mice remains unaltered. In contrast, EtOH consumption significantly reduces the ability of CD8 T cells to degranulate and kill IAV-specific targets. Finally, our findings suggest the lesion begins during the initial activation of CD8 T cells, as we observe early defects in proliferation in the dLN of IAV-infected, EtOH-consuming mice. These findings highlight the previously unrecognized depth of the lesion in the IAV-specific CD8 T cell response during chronic EtOH consumption. Given the important role CD8 T cell immunity plays in control of IAV, these findings may aid in the development of vaccination and/or therapeutic strategies to reverse these defects in the CD8 T cell response and reduce serious disease outcomes associated with IAV infections in alcoholics.

Fetal ethanol exposure and the developing alveolar macrophage

Excessive consumption of alcohol (EtOH), the 3 leading preventable cause of death in the USA, has been shown to lead to increased incidence and severity of acute respiratory distress syndrome. The increased risk of respiratory infections in alcoholics is believed to be due to alterations in alveolar macrophage (AM) function. Previous studies have shown chronic EtOH ingestion leads to increased oxidant stress, increased TGFb production, increased fibronectin production, and decreased phagocytosis in AMs. Alternative (M2) activation of AMs has also been shown to lead to similar alterations. Classical ‘‘M1’’ by T helper 1 (TH1) cytokines leads to a proinflammatory response that is required for the respiratory burst necessary for phagocytosis. However, M2 is induced by TH2 cytokines leads to increased arginase production, increased arginase activity, and increased proline and polyamine production. These events promote fibroblast proliferation, collagen production and fibrosis within the lung. Our aim was to determine if chronic EtOH treatment leads to alterations in the expression of markers of M2 activation in AMs. To test this hypothesis, NR8383 cells, a rat-derived alveolar macrophage cell line, were treated with 0.08% EtOH, 25mM acetylaldehyde (AA), or IL-13, a know activator of M2 activation, 6 GSH or 6 IL-13 neutralizing antibody for 5 days. The cells were then analyzed for arginase activity and expression, active TGF-b production in cell culture media, and fibronectin production by 3T3 cells, a fibroblast cell line. In NR8383 cells, treatment with EtOH, AA, or IL-13 led to increased arginase activity, increased arginase expression, active TGF-b production, and secretion of factors that promoted fibronectin production in 3T3 cells. Supplementation with GSH or IL-13 neutralizing antibody during the 5 day treatment led to partial normalization of arginase activity, arginase expression, active TGF-b production, and activation of 3T3 cells in fibronectin production. In conclusion, several markers of M2 activation were greatly increased in response to EtOH, AA, and IL-13 treatment and GSH/ IL-13 neutralizing antibody treatment blocked these effects suggesting chronic EtOH treatment leads to M2 activation of AMs and antioxidant treatment can partially prevent that switch.

Hepatitis C Virus and Alcohol

This review will focus on the prevalence of hepatitis c virus (HCV) infection in alcoholics with and without liver disease. Evidence will be presented to demonstrate that ethanol and chronic HCV infection synergistically accelerate liver injury. Some of the major postulated mechanisms responsible for disease progression include high rates of apoptosis, lipid peroxidation, and generation of free radicals and reactive oxygen species with reduced antioxidant capacity of the liver. Acquisition and persistence of HCV infection may be due to the adverse effects of ethanol on humoral and cellular immune responses to HCV. Dendritic cells (DC) appear to be one of the major targets for ethanol's action and DC dysfunction impairs the ability of the host to generate viral specific cluster of differentiation 4 (CD4+) and cluster of differentiation 8 (CD8+) immune responses. There is a relationship between increased alcohol intake and decreased response to interferon (IFN) therapy, which may be reversed by abstinence. Clinical studies are needed to optimize treatment responses in alcoholic patients with chronic HCV infection.

An evaluation of fetal/neonatal and chronic adult ethanol exposure (FNEE and CAEE) on murine cutaneous dendritic cell (CDC) maturation and migration using an organ culture system (92.5)

Abstract Alcoholism and fetal alcohol syndrome are associated with increased rates of infection. CDCs, consisting of Langerhans cells (LCs), langerin+ dermal dendritic cells (LdDCs) and langerin - dermal dendritic cells, initiate adaptive immune responses by transporting antigen from the skin to the regional lymph node (RLN). We previously reported a migratory delay of langerin+ CDCs (LCDCs) into the RLN due to CAEE. Migration of CDCs into the RLN is driven by chemokine receptors (CCRs) and adhesion molecules (AMs). To determine if either CAEE or FNEE impair the CCR/AM expression needed for timely transit into the RLN, skin explants were cultured (+/-) CPG & CCL21, and the phenotypes of emigrated CDCs (eCDCs) from control and EtOH exposed mice were evaluated by flow cytometry. CAEE reduced the numbers of emigrated LCs (eLCs). It also reduced CCR7 expression on eLCs and emigrated LdDCs (eLdDCs) and LFA-1 expression on eLdDCs. In contrast, FNEE induced a trend towards increased numbers of eLCs without affecting CCR7 and LFA-1 expression. These findings suggest that diminished CDC migratory capacity is a result of CAEE and not FNEE. The decreased expression of CCR7 and LFA-1 provides a mechanism for the migratory delay exhibited by LCDCs as a result of CAEE and ultimately, a mechanism to explain increased skin infections in alcoholics. Evaluation of additional AMs/CCRs are underway for both models. NIH RO1 AA014405 and AA014406 supported this work.

Hepatitis C virus and ethanol alter antigen presentation in liver cells

Alcoholic patients have a high incidence of hepatitis C virus (HCV) infection. Alcohol consumption enhances the severity of the HCV disease course and worsens the outcome of chronic hepatitis C. The accumulation of virally infected cells in the liver is related to the HCV-induced inability of the immune system to recognize infected cells and to develop the immune responses. This review covers the effects of HCV proteins and ethanol on major histocompatibility complex (MHC) class I- and class II-restricted antigen presentation. Here, we discuss the liver which functions as an immune privilege organ; factors, which affect cleavage and loading of antigenic peptides onto MHC class I and class II in hepatocytes and dendritic cells, and the modulating effects of ethanol and HCV on antigen presentation by liver cells. Altered antigen presentation in the liver limits the ability of the immune system to clear HCV and infected cells and contributes to disease progression. HCV by itself affects dendritic cell function, switching their cytokine profile to the suppressive phenotype of interleukin-10 (IL-10) and transforming growth factor beta (TGFbeta) predominance, preventing cell maturation and allostimulation capacity. The synergistic action of ethanol with HCV results in the suppression of MHC class II-restricted antigen presentation. In addition, ethanol metabolism and HCV proteins reduce proteasome function and interferon signaling, thereby suppressing the generation of peptides for MHC class I-restricted antigen presentation. Collectively, ethanol exposure further impairs antigen presentation in HCV-infected liver cells, which may provide a partial explanation for exacerbations and the poor outcome of HCV infection in alcoholics.

Occult HBV infection—both hidden and mysterious

Occult HBV infection—both hidden and mysterious

Prevalence of intestinal nematodes in alcoholic patients.

We report the results of a retrospective study on the frequency of intestinal nematodes among 198 alcoholic and 440 nonalcoholic patients at the University Hospital Cassiano Antonio Moraes in Vit ria, ES, Brazil. The control sample included 194 nonalcoholic patients matched according to age, sex and neighborhood and a random sample of 296 adults admitted at the same hospital. Stool examination by sedimentation method (three samples) was performed in all patients. There was a significantly higher frequency of intestinal nematodes in alcoholics than in controls (35.3% and 19.2%, respectively), due to a higher frequency of Strongyloides stercoralis (21.7% and 4.1%, respectively). Disregarding this parasite, the frequency of the other nematodes was similar in both groups. The higher frequency of S. stercoralis infection in alcoholics could be explained by immune modulation and/or by some alteration in corticosteroid metabolism induced by chronic ethanol ingestion. Corticosteroid metabolites would mimic the worm ecdisteroids, that would in turn increase the fecundity of females in duodenum and survival of larvae. Consequently, the higher frequency of Strongyloides larvae in stool of alcoholics does not necessarily reflect an increased frequency of infection rate, but only an increased chance to present a positive stool examination using sedimentation methods.

Frequency of Strongyloides stercoralis infection in alcoholics.

Several studies have shown that chronic alcoholics have increased susceptibility to infections due to higher exposure to infectious agents as well as breakdown in their immune defenses. As Strongyloides stercoralis infection is usually more relevant in immunocompromised patients, the aim of this study was to evaluate the frequency of S. stercoralis infection in alcoholics. Thus, coproparasitological examination was carried out in 145 subjects, from which 45 were chronic alcoholics (mean age of 45.7 +/- 11.0 years), 10 were nonalcoholic cirrhotic patients (mean age of 50.2 +/- 13.1 years), and 90 were asymptomatic nonalcoholic subjects (mean age of 46.7 +/- 10.1 years), which served as controls. From the alcoholics, 9 had hepatic cirrhosis, 9 had chronic pancreatitis and 27 had neither cirrhosis nor pancreatitis. For the diagnosis of strongyloidiasis, the Baermann-Moraes and Lutz methods were used in three fecal samples from each subject. Samples were collected at alternated days, and three slides of each sample were analyzed for each method, thus totalizing 2,610 slides examined. The frequency of strongloidiasis in the total alcoholic group (33.3%) and in the subgroups of alcoholics, i.e., patients with hepatic cirrhosis (44.4%), with chronic pancreatitis (33.3%), and those with no cirrhosis or pancreatitis (29.6%) was statistically higher than that found in the control group (5.5%). None of the individuals with nonalcoholic hepatic cirrhosis had S. stercoralis infection. Our results showed that the chronic alcoholism itself is an important factor that predisposes to strongyloidiasis.

Hepatitis c virus (HCV) and human immunodeficiency virus type 1 (HIV-1) infections in alcoholics

Approximately 400,000 individuals in the United States are co-infected with hepatitis C virus (HCV) and human immunodeficiency virus type 1 (HIV-1) and it is likely that almost one in two of these subjects consumes alcohol. The majority of these patients suffer an accelerated course of liver disease as manifested by the onset of cirrhosis within 5 to 10 years of developing HCV infection, as well as an increased risk of developing hepatocellular carcinoma (HCC). It is thought that chronic alcohol abuse mediates liver damage as a result of increased production of free radicals and proinflammatory cytokines. In the setting of chronic HCV infection, alcohol ingestion has an additional effect of diminishing immune clearance and increasing viral burden to hasten the onset of cirrhosis and HCC. Likewise, chronic HCV and HIV-1 co-infection results in a net increase in HCV burden; higher prevalence rates of HCV transmission to sexual partners and offspring, as well as an accelerated progression to end stage liver disease as compared to individuals with HCV infection alone. Thus, the synergistic effects of alcohol abuse and HIV-1 greatly impact on the morbidity and mortality for patients with HCV coinfection. Ultimately, this cumulative disease process will require far more aggressive management with abstinence and counseling for alcohol abuse; highly active antiretroviral therapy (HAART) for HIV infection and combination anti-viral therapy for HCV infection to stem the rapid progression to end stage liver disease.

Molecular regulation of iron homeostasis and resistance to infection in alcoholics.

Chronic alcohol abuse is associated with both an altered response to infection and deranged iron homeostasis. While both clinical manifestations are well known, the inter-relationships between alcohol and iron and the response to infection are not. The recent identification of a plethora of iron regulatory and transport proteins has now begun to explain these relationships. This article outlines the current state of knowledge on cellular iron homeostasis, with particular reference to the iron regulatory proteins (IRP1, IRP2 and HFE) and the iron membrane transport proteins, two of which have been shown to be members of the natural resistance- associated macrophage protein family (Nramp1 and 2). Following this introduction, the response of the body to infection, in terms of iron withholding is discussed at the cellular level, especially in terms of the macrophage and its cytokine-mediated responses. Prior alterations to body iron status are also considered in this section. The effect of alcohol alone on the body's response to infection is then outlined, principally in terms of the macrophage function and cytokine regulation. These are then combined to correlate the clinical and experimental observations with known derangements produced by the individual insults of alcohol and altered iron homeostasis. on the response to infection. Particular attention is paid not only to cytokine/chemokine actions, but also to the consequences of the altered production of reactive oxygen and nitrogen species. Finally, the possible mechanisms by which alcohol and altered iron homeostasis lead to tissue damage during infection.

Hepatitis C virus (HCV) and human immunodeficiency virus type 1 (HIV-1) infections in alcoholics.

Approximately 400,000 individuals in the United States are co-infected with hepatitis C virus (HCV) and human immunodeficiency virus type 1 (HIV-1) and it is likely that almost one in two of these subjects consumes alcohol. The majority of these patients suffer an accelerated course of liver disease as manifested by the onset of cirrhosis within 5 to 10 years of developing HCV infection, as well as an increased risk of developing hepatocellular carcinoma (HCC). It is thought that chronic alcohol abuse mediates liver damage as a result of increased production of free radicals and proinflammatory cytokines. In the setting of chronic HCV infection, alcohol ingestion has an additional effect of diminishing immune clearance and increasing viral burden to hasten the onset of cirrhosis and HCC. Likewise, chronic HCV and HIV-1 co-infection results in a net increase in HCV burden; higher prevalence rates of HCV transmission to sexual partners and offspring, as well as an accelerated progression to end stage liver disease as compared to individuals with HCV infection alone. Thus, the synergistic effects of alcohol abuse and HIV-1 greatly impact on the morbidity and mortality for patients with HCV coinfection. Ultimately, this cumulative disease process will require far more aggressive management with abstinence and counseling for alcohol abuse; highly active antiretroviral therapy (HAART) for HIV infection and combination anti-viral therapy for HCV infection to stem the rapid progression to end stage liver disease.

Molecular regulation of iron homeostasis and resistance to infection in alcoholics

Chronic alcohol abuse is associated with both an altered response to infection and deranged iron homeostasis. While both clinical manifestations are well known, the inter-relationships between alcohol and iron and the response to infection are not. The recent identification of a plethora of iron regulatory and transport proteins has now begun to explain these relationships. This article outlines the current state of knowledge on cellular iron homeostasis, with particular reference to the iron regulatory proteins (IRP1, IRP2 and HFE) and the iron membrane transport proteins, two of which have been shown to be members of the natural resistance- associated macrophage protein family (Nramp1 and 2). Following this introduction, the response of the body to infection, in terms of iron withholding is discussed at the cellular level, especially in terms of the macrophage and its cytokine-mediated responses. Prior alterations to body iron status are also considered in this section. The effect of alcohol alone on the body's response to infection is then outlined, principally in terms of the macrophage function and cytokine regulation. These are then combined to correlate the clinical and experimental observations with known derangements produced by the individual insults of alcohol and altered iron homeostasis. on the response to infection. Particular attention is paid not only to cytokine/chemokine actions, but also to the consequences of the altered production of reactive oxygen and nitrogen species. Finally, the possible mechanisms by which alcohol and altered iron homeostasis lead to tissue damage during infection.

Effects of ethanol on NF-kappaB activation, production of myeloid growth factors, and adhesive events in human endothelial cells.

Because neutropenia may aggravate infections in alcoholics, effects of ethanol on the generation of myeloid growth factors by human umbilical vein endothelial cells (HUVECs) and on interactions with neutrophils were examined in vitro. Exposure of HUVECs to ethanol (0.01%-1%) dose-dependently inhibited (by 12%-27%) the release of stem cell factor, granulocyte-macrophage and granulocyte colony-stimulating factors (CSFs), or interleukin (IL)-8, but not of macrophage CSF triggered by lipopolysaccharide (LPS) or IL-1. Ethanol also inhibited the LPS-induced increase in HUVECs to bind neutrophils by 28% (without affecting the expression of intracellular adhesion molecule-1 and E-selectin) and inhibited the translocation of the p65 subunit of NF-kappaB from the cytoplasm to the nucleus by 46%. Thus, exposure of HUVECs to ethanol inhibited the generation of cytokines important for myeloid cell development and reduced the adhesiveness of HUVECs for neutrophils: effects that are possibly linked to the reduced activation of NF-kappaB.

Prevalence of human immunodeficiency virus infection in alcoholics.

To verify the prevalence of infection by human immunodeficiency virus (HIV) in alcoholics we studied 131 alcoholic patients (119 males and 12 females) with a mean age of 44.3 +/- 10.8 years. Serum samples were collected from this group and analysed, by ELISA, for antibodies against HIV as well as for serological markers for hepatitis B virus (HBV) and hepatitis C virus (HCV). As we have previously described, we found a high prevalence of HBV (26.4%) and HCV (4.2%) markers as compared to the prevalence of these markers in samples of normal blood donors from Uberlândia's Hemocentro Regional, which are 4% and 0.4%, respectively. Of the 131 patients, four (3%) had antibodies against HIV, three (75%) of which were injecting drug users (IDU). In the HIV-negative group, only one patient was an IDU. The prevalence of HIV in our population, according to data from the city's Health Secretary, varies from 3.1% to 6.2%. We conclude that, at least for the moment, alcoholism per se, did not constitute an important risk factor for HIV infection. However, acquired immunodeficiency syndrome is a rather recent disease as compared to hepatitis B and C and, as the transmission routes are similar for HIV and hepatitis viruses, an increase in the incidence of HIV infection in alcoholics may be just a question of time.

Ethanol Inhibition: The Humoral and Cellular Immune Response to Hepatitis C Virus NS5 Protein After Genetic Immunization

The combination of chronic hepatitis C virus (HCV) and ethanol may increase viral replication, impair cellular immunity, and result in severe and progressive liver disease. Because HCV nonstructural proteins play a major role in viral elimination, we examined the cellular and humoral immune responses after genetic immunization against NS5 in a chronic ethanol mouse model. Mice were fed an ethanol or isocaloric pair-fed control liquid diet and were immunized with HCV NS5-expression plasmid. The humoral and cellular arms of the immune system were significantly impaired in ethanol-fed mice. Abstinence partially reversed the inhibitory effects on antibody levels and the CD4+ proliferative immune response but did not restore the CD8+ cytotoxic T-cell response to this HCV nonstructural protein. Furthermore, we determined whether murine interleukin-2 coadministration with the NS5 expression plasmid would reverse the inhibitory effects of chronic ethanol consumption; again, partial restoration was observed for B-cell and CD4+ T-cell activity, but not for cytotoxic T cells. These results suggest that the high rate of chronic HCV infection in alcoholics may be due to ethanol's effects on antiviral immune responses.

Isotonic ethanol inhibits the generation of superoxide anion in neutrophils by inducing cell expansion

The effects of ethanol on the production of oxygen-derived free radicals by neutrophils are controversial. Osmolarity-mediated alteration of cell volume appears to be an important mechanism for regulating neutrophil activity. We investigated in neutrophils from healthy volunteers the effect of isotonic/hypertonic ethanol on both chemiluminescence amplified by a Cypridina luciferin analog in response to N-formyl-Met-Lue-Phe and cell volume measured with a Coulter counter. Both isotonic and hypertonic ethanol significantly decreased chemiluminescence in a dose-dependent manner. Isotonic ethanol produced a greater magnitude of inhibition than hypertonic ethanol (P < 0.01). Another permeable molecule, urea, and hypotonic solution had the same effects on chemiluminescence. Isotonic and hypertonic ethanol caused a prompt cell expansion and shrinking, respectively. On the other hand, isotonic sucrose, an impermeable molecule, was ineffective in both chemiluminescence and cell volume changes. These data suggest that isotonic ethanol inhibits the superoxide anion production by inducing cell expansion probably due to increased intracellular osmotic pressure caused by rapid ethanol permeation through the plasmalemma. This impaired neutrophil function may, in some part, contribute to the susceptibility to infection in alcoholics.