RESUMO
BACKGROUND: Delayed CD4 recovery after initiating antiretroviral therapy (ART) is a novel potential mechanism by which alcohol consumption leads to increased morbidity and mortality in people with HIV. We hypothesized that alcohol consumption at ART initiation is associated with slower CD4 recovery. METHODS: We retrospectively analyzed 2 pooled longitudinal alcohol/HIV cohorts (2014-2019) in St. Petersburg, Russia. Eligible participants initiated the first ART during parent studies; had alcohol consumption assessed by the blood biomarker, phosphatidylethanol (PEth), at the last research visit before ART initiation; and had ≥1 CD4 count measurement before and after initiating ART. Participants were stratified by low, moderate, and high PEth (<8, 8-80, and >80 ng/mL, respectively). We used random-effects piecewise linear regression models to estimate CD4 recovery, defined as CD4 count change per 30 days after ART initiation, by the alcohol group. RESULTS: Of 60 eligible participants, median age was 34 years and 28% were female. The median pre-ART PEth in the low, moderate, and high PEth groups were <8, 23, and 232 ng/mL, respectively. After starting ART, the CD4 count increased by 13.60 cells/mm3/mo (95% CI: 0.33 to 26.87) with low PEth, 0.93 cells/mm3/mo (95% CI: -6.18 to 8.04) with moderate PEth, and 2.33 cells/mm3/mo (95% CI: -3.44 to 8.09) with high PEth. CONCLUSIONS: Among Russians with HIV, we observed faster CD4 recovery after ART initiation in those with low alcohol consumption compared with those with moderate and high alcohol consumption, as assessed by PEth. This analysis provides further evidence for the possible value of alcohol reduction interventions for people with HIV who are initiating ART.
Assuntos
Consumo de Bebidas Alcoólicas , Antirretrovirais , Antígenos CD4 , Contagem de Linfócito CD4 , Infecções por HIV , Adulto , Feminino , Humanos , Masculino , Consumo de Bebidas Alcoólicas/efeitos adversos , Consumo de Bebidas Alcoólicas/imunologia , Etanol , Infecções por HIV/complicações , Infecções por HIV/tratamento farmacológico , Estudos Retrospectivos , Federação Russa/epidemiologia , Antirretrovirais/efeitos adversos , Antirretrovirais/imunologia , Antígenos CD4/imunologiaRESUMO
PURPOSE: In clinical practice, currently one reference range for serum immunoglobulin (Ig) A, G, and M is applied to all adults, although various factors may influence Ig serum levels. Population-based data on determinants of IgA, IgG, and IgM and recommendations for subgroup specific reference ranges are lacking. We aimed to provide an overview of determinants of IgA, IgG, and IgM in community-dwelling middle-aged and elderly individuals and explore determinants that influence Ig reference ranges. METHODS: Within the Rotterdam Study, we performed linear regression analyses for the association of demographic, lifestyle, and cardiovascular factors with serum IgA, IgG, and IgM. We furthermore calculated Ig reference ranges (based on percentiles), both overall and within relevant subgroups. RESULTS: We included 8768 participants (median age 62 years). IgA and IgG increased non-linearly with higher age (P < .0001 for both). Women had lower IgA (beta: - 0.24; 95% confidence interval [95% CI]: - 0.29; - 0.20) and IgG (beta: - 0.33; 95% CI: - 0.44; - 0.23), but higher IgM levels (beta: 0.08; 95% CI: 0.04;0.13) than men. Former and particularly current smoking were associated with lower IgA and IgG (betas between - 0.07 and - 1.03). Higher alcohol consumption was associated with lower IgG (beta for heavy drinking: - 0.70; 95% CI: - 0.91; - 0.48). Corticosteroid use was associated with lower IgG (beta: - 1.12; 95% CI: - 1.58; - 0.66). Associations with cardiovascular factors were heterogeneous and differed between sexes. CONCLUSION: Age, sex, smoking, alcohol consumption, corticosteroid use, and cardiovascular factors are determinants that should be considered when interpreting serum Ig levels in middle-aged and elderly individuals and may require adjusted reference ranges.
Assuntos
Imunoglobulina A/sangue , Imunoglobulina G/sangue , Imunoglobulina M/sangue , Corticosteroides/uso terapêutico , Fatores Etários , Idoso , Consumo de Bebidas Alcoólicas/sangue , Consumo de Bebidas Alcoólicas/imunologia , Feminino , Fatores de Risco de Doenças Cardíacas , Humanos , Estilo de Vida , Masculino , Pessoa de Meia-Idade , Valores de Referência , Fatores Sexuais , Fumar/sangue , Fumar/imunologiaRESUMO
Alcohol binge drinking (BD) and poor nutritional habits are two frequent behaviors among many adolescents that alter gut microbiota in a pro-inflammatory direction. Dysbiotic changes in the gut microbiome are observed after alcohol and high-fat diet (HFD) consumption, even before obesity onset. In this study, we investigate the neuroinflammatory response of adolescent BD when combined with a continuous or intermittent HFD and its effects on adult ethanol consumption by using a self-administration (SA) paradigm in mice. The inflammatory biomarkers IL-6 and CX3CL1 were measured in the striatum 24 h after BD, 3 weeks later and after the ethanol (EtOH) SA. Adolescent BD increased alcohol consumption in the oral SA and caused a greater motivation to seek the substance. Likewise, mice with intermittent access to HFD exhibited higher EtOH consumption, while the opposite effect was found in mice with continuous HFD access. Biochemical analyses showed that after BD and three weeks later, striatal levels of IL-6 and CX3CL1 were increased. In addition, in saline-treated mice, CX3CL1 was increased after continuous access to HFD. After oral SA procedure, striatal IL-6 was increased only in animals exposed to BD and HFD. In addition, striatal CX3CL1 levels were increased in all BD- and HFD-exposed groups. Overall, our findings show that adolescent BD and intermittent HFD increase adult alcohol intake and point to neuroinflammation as an important mechanism modulating this interaction.
Assuntos
Consumo de Bebidas Alcoólicas/metabolismo , Consumo Excessivo de Bebidas Alcoólicas/fisiopatologia , Fatores Etários , Consumo de Bebidas Alcoólicas/imunologia , Consumo de Bebidas Alcoólicas/prevenção & controle , Animais , Animais não Endogâmicos , Consumo Excessivo de Bebidas Alcoólicas/metabolismo , Quimiocina CXCL1/metabolismo , Dieta Hiperlipídica , Etanol/farmacologia , Inflamação/metabolismo , Interleucina-6/metabolismo , Masculino , Camundongos , Obesidade , Autoadministração/métodosRESUMO
Ethanol consumption represents a significant public health problem, and excessive ethanol intake is a risk factor for cardiovascular disease (CVD), one of the leading causes of death and disability worldwide. The mechanisms underlying the effects of ethanol on the cardiovascular system are complex and not fully comprehended. The gut microbiota and their metabolites are indispensable symbionts essential for health and homeostasis and therefore, have emerged as potential contributors to ethanol-induced cardiovascular system dysfunction. By mechanisms that are not completely understood, the gut microbiota modulates the immune system and activates several signaling pathways that stimulate inflammatory responses, which in turn, contribute to the development and progression of CVD. This review summarizes preclinical and clinical evidence on the effects of ethanol in the gut microbiota and discusses the mechanisms by which ethanol-induced gut dysbiosis leads to the activation of the immune system and cardiovascular dysfunction. The cross talk between ethanol consumption and the gut microbiota and its implications are detailed. In summary, an imbalance in the symbiotic relationship between the host and the commensal microbiota in a holobiont, as seen with ethanol consumption, may contribute to CVD. Therefore, manipulating the gut microbiota, by using antibiotics, probiotics, prebiotics, and fecal microbiota transplantation might prove a valuable opportunity to prevent/mitigate the deleterious effects of ethanol and improve cardiovascular health and risk prevention.
Assuntos
Consumo de Bebidas Alcoólicas/fisiopatologia , Doenças Cardiovasculares/fisiopatologia , Disbiose/fisiopatologia , Microbioma Gastrointestinal , Consumo de Bebidas Alcoólicas/imunologia , Antibacterianos/uso terapêutico , Anti-Infecciosos Locais , Doenças Cardiovasculares/imunologia , Doenças Cardiovasculares/terapia , Disbiose/imunologia , Disbiose/terapia , Etanol , Transplante de Microbiota Fecal , Humanos , Prebióticos , Probióticos/uso terapêuticoRESUMO
Traumatic injuries afflict more than 5 million people globally every year. Current and past animal research has demonstrated association among alcohol, trauma, and impaired immune function, whereas human registries have shown association between alcohol and morbidity as well as mortality. The purpose of this study is to elucidate the immune interactions with alcohol in traumatically injured patients. We prospectively enrolled 379 patients after trauma at three medical centers in the Surgical Critical Care Initiative. Plasma was analyzed using Luminex for up to 35 different cytokines. Collected samples were grouped by patients with detectable plasma alcohol levels versus those without. Univariate testing determined differences in analytes between groups. We built Bayesian belief networks with multiple minimum descriptive lengths to compare the two groups. All 379 patient samples were analyzed. Two hundred eighty-two (74.4%) patients were men, and 143 (37.7%) were White. Patients had a median intensive care unit length of stay (LOS) of 5.8 days and hospital LOS of 12 days. Using single variate analyses, eight different cytokines were differentially associated with alcohol. Cytokines IL-12 and IL-6 were important nodes in both models and IL-10 was a prominent node in the nonalcohol model. This study found select immune function differed between traumatically injured patients with measurable serum alcohol levels as compared with those without. Traumatically injured patients with positive blood alcohol content appear less able to inhibit inflammatory stress. Alcohol appears to suppress pro-inflammatory IL-12 and IL-6, whereas patients without alcohol have greater levels of anti-inflammatory IL-10 expressed at injury and may better regulate anti-inflammatory pathways. Future studies should determine the relationship with these markers with clinically oriented outcomes.
Assuntos
Consumo de Bebidas Alcoólicas/imunologia , Etanol/efeitos adversos , Transdução de Sinais/efeitos dos fármacos , Ferimentos e Lesões/imunologia , Adulto , Consumo de Bebidas Alcoólicas/efeitos adversos , Consumo de Bebidas Alcoólicas/sangue , Teorema de Bayes , Feminino , Humanos , Interleucina-10/sangue , Interleucina-10/imunologia , Interleucina-12/sangue , Interleucina-12/imunologia , Interleucina-6/sangue , Interleucina-6/imunologia , Tempo de Internação/estatística & dados numéricos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Transdução de Sinais/imunologia , Ferimentos e Lesões/sangueRESUMO
Benefits and harms of different components of human diet have been known for hundreds of years. Alcohol is one the highest consumed, abused, and addictive substances worldwide. Consequences of alcohol abuse are increased risks for diseases of the cardiovascular system, liver, and nervous system, as well as reduced immune system function. Paradoxically, alcohol has also been a consistent protective factor against the development of autoimmune diseases such as type 1 diabetes, multiple sclerosis, systemic lupus erythematosus, and rheumatoid arthritis (RA). Here, we focused on summarizing current findings on the effects of alcohol, as well as of its metabolites, acetaldehyde and acetate, on the immune system and RA. Heavy or moderate alcohol consumption can affect intestinal barrier integrity, as well as the microbiome, possibly contributing to RA. Additionally, systemic increase in acetate negatively affects humoral immune response, diminishing TFH cell as well as professional antigen-presenting cell (APC) function. Hence, alcohol consumption has profound effects on the efficacy of vaccinations, but also elicits protection against autoimmune diseases. The mechanism of alcohol's negative effects on the immune system is multivariate. Future studies addressing alcohol and its metabolite acetate's effect on individual components of the immune system remains crucial for our understanding and development of novel therapeutic pathways.
Assuntos
Consumo de Bebidas Alcoólicas/imunologia , Artrite Reumatoide/imunologia , Etanol/farmacologia , Sistema Imunitário/efeitos dos fármacos , Substâncias Protetoras/farmacologia , Acetaldeído/imunologia , Acetaldeído/farmacologia , Acetatos/imunologia , Acetatos/farmacologia , Etanol/imunologia , HumanosRESUMO
AIMS: In the course of the COVID-19 pandemic, multiple suggestions have been delivered through websites and social media referring to natural substances and various kinds of supplements with thaumaturgical properties in preventing and/or fighting the coronavirus infection. Indeed, there is no clinical trial evidence that a dietary or pharmacological supplementation of any particular substance will increase the effectiveness of the immune defences. There are however three nutritional issues that deserve special attention under the present circumstances, namely vitamin D deficiency, excess salt intake and inappropriate alcohol consumption. Here is a short review of the current knowledge about the possible role of these factors in the immunity defence system and their potential impact on the modulation of the immune response to SARS-COV2 infection. DATA SYNTHESIS: For all of these factors there is convincing evidence of an impact on the immune defence structure and function. In the absence of RCT demonstration that increased ingestion of any given substance may confer protection against the new enemy, special attention to correction of these three nutritional criticisms is certainly warranted at the time of COVID pandemic. CONCLUSIONS: We propose that the inappropriate intake of salt and alcohol and the risk of inadequate vitamin D status should be object of screening, in particular in subjects at high mortality risk from SARS-COV 2 infection, such as institutionalised elderly subjects and all those affected by predisposing conditions.
Assuntos
Consumo de Bebidas Alcoólicas/epidemiologia , COVID-19/imunologia , Estado Nutricional , Sódio na Dieta/efeitos adversos , Deficiência de Vitamina D/epidemiologia , Consumo de Bebidas Alcoólicas/imunologia , COVID-19/epidemiologia , Dieta/métodos , Suplementos Nutricionais , Humanos , Imunidade , Pandemias , Saúde Pública , Fatores de Risco , SARS-CoV-2 , Vitamina D/administração & dosagem , Deficiência de Vitamina D/imunologia , Deficiência de Vitamina D/terapia , Vitaminas/administração & dosagemRESUMO
The intestinal microbiome is an essential so-called human "organ", vital for the induction of innate immunity, for metabolizing nutrients, and for maintenance of the structural integrity of the intestinal barrier. HIV infection adversely influences the richness and diversity of the intestinal microbiome, resulting in structural and functional impairment of the intestinal barrier and an increased intestinal permeability. Pathogens and metabolites may thus cross the "leaky" intestinal barrier and enter the systemic circulation, which is a significant factor accounting for the persistent underlying chronic inflammatory state present in people living with HIV (PLWH). Additionally, alcohol use and abuse has been found to be prevalent in PLWH and has been strongly associated with the incidence and progression of HIV/AIDS. Recently, converging evidence has indicated that the mechanism underlying this phenomenon is related to intestinal microbiome and barrier function through numerous pathways. Alcohol acts as a "partner" with HIV in disrupting microbiome ecology, and thus impairing of the intestinal barrier. Optimizing the microbiome and restoring the integrity of the intestinal barrier is likely to be an effective adjunctive therapeutic strategy for PLWH. We herein critically review the interplay among HIV, alcohol, and the gut barrier, thus setting the scene with regards to development of effective strategies to counteract the dysregulated gut microbiome and the reduction of microbial translocation and inflammation in PLWH.
Assuntos
Consumo de Bebidas Alcoólicas/imunologia , Alcoolismo/imunologia , Disbiose/imunologia , Infecções por HIV/imunologia , HIV/imunologia , Mucosa Intestinal/imunologia , Microbioma Gastrointestinal/imunologia , HumanosRESUMO
BACKGROUND: Excessive UV radiation disrupts skin homeostasis by multiple mechanisms that extend beyond the simple erythema associated with sunburns including reduction of antioxidants, increased DNA damage, and impairment of skin immune responses. Recreational UV exposure frequently occurs concurrently with excessive ethanol (EtOH). Epidemiological studies suggest a harmful, dose-dependent impact of EtOH in the setting of high UV exposure, leading to increased severity of sunburns relative to those generated in the absence of EtOH. Furthermore, EtOH consumption and UV radiation have multiple overlapping effects on the skin that could account for the epidemiological association. OBJECTIVE: To elucidate the relationship between excessive EtOH ingestion and UV exposures on early skin damage and downstream immune dysfunction. METHODS: We examined the impact of UVB on local skin damage, including inflammation, sunburned cells, apoptotic cells, melanin and antioxidant levels, DNA damage and immune dysfunction in the presence or absence of EtOH ingestion by combining standard mouse models of EtOH consumption and UVB exposure models. To confirm that the observed changes in mouse skin were relevant to human skin, we investigated the effects of EtOH on UV-induced skin damage with human skin explants. RESULTS: We demonstrated that EtOH consumption and UV exposure act synergistically to increase the severity of local skin damage resulting in impaired melanin responses, reduced antioxidants, greater DNA damage, and immune dysfunction as measured by reduced contact hypersensitivity. CONCLUSIONS: The results support incorporation of the risks of combined UV exposure and excessive alcohol consumption into public health campaigns.
Assuntos
Consumo de Bebidas Alcoólicas/efeitos adversos , Neoplasias Cutâneas/prevenção & controle , Pele/imunologia , Queimadura Solar/diagnóstico , Raios Ultravioleta/efeitos adversos , Consumo de Bebidas Alcoólicas/imunologia , Consumo de Bebidas Alcoólicas/prevenção & controle , Animais , Dano ao DNA/efeitos dos fármacos , Dano ao DNA/imunologia , Dano ao DNA/efeitos da radiação , Modelos Animais de Doenças , Etanol/efeitos adversos , Feminino , Educação em Saúde , Humanos , Recém-Nascido , Masculino , Camundongos , Índice de Gravidade de Doença , Pele/patologia , Pele/efeitos da radiação , Neoplasias Cutâneas/imunologia , Neoplasias Cutâneas/patologia , Queimadura Solar/imunologia , Queimadura Solar/patologia , Técnicas de Cultura de TecidosRESUMO
Prior research on alcohol and the immune system has tended to focus on binge doses or chronic heavy drinking. The aim of this single-session preliminary study was to characterize immune response to moderate alcohol (0.60 g alcohol per kilogram body weight) in healthy, nonchronic drinkers. The sample (N = 11) averaged 26.6 years of age and was balanced in gender. Plasma samples were collected at baseline and 1, 2 and 3 hours postconsumption. Markers of microbial translocation [lipopolysaccharide (LPS)] and innate immune response [LPS-binding protein (LBP), soluble cluster of differentiation 14 (sCD14), and selected cytokines] were measured using immunoassays. Participants completed self-report questionnaires on subjective alcohol response and craving. Linear mixed models were used to assess changes in biomarkers and self-report measures. Breath alcohol concentration peaked at 0.069 ± 0.008% 1 hour postconsumption. LPS showed a significant linear decrease. LBP and sCD14 showed significant, nonlinear (U-shaped) trajectories wherein levels decreased at 1 hour then rebounded by 3 hours. Of nine cytokines tested, only MCP-1 and IL-8 were detectable in ≥50% of samples. IL-8 did not change significantly. MCP-1 showed a significant linear decrease and also accounted for significant variance in alcohol craving, with higher levels associated with stronger craving. Results offer novel evidence on acute immune response to moderate alcohol. Changes in LBP and sCD14, relative to LPS, may reflect their role in LPS clearance. Results also support further investigation into the role of MCP-1 in alcohol craving. Limitations include small sample size and lack of a placebo condition.
Assuntos
Consumo de Bebidas Alcoólicas/imunologia , Fissura/efeitos dos fármacos , Etanol/administração & dosagem , Imunidade/efeitos dos fármacos , Mediadores da Inflamação/imunologia , Adulto , Consumo de Bebidas Alcoólicas/sangue , Consumo de Bebidas Alcoólicas/psicologia , Biomarcadores/sangue , Concentração Alcoólica no Sangue , Fissura/fisiologia , Feminino , Voluntários Saudáveis , Humanos , Imunidade/fisiologia , Mediadores da Inflamação/sangue , Masculino , Autorrelato , Adulto JovemRESUMO
BACKGROUND: The inbred mouse strain C57BL/6 is widely used in both models of addiction and immunological disease. However, there are pronounced phenotypic differences in ethanol (EtOH) consumption and innate immune response between C57BL/6 substrains. The focus of this study was to examine the effects of substrain on innate immune response and neuroimmune-induced escalation of voluntary EtOH consumption. The main goal was to identify whether substrain differences in immune response can account for differences in EtOH behavior. METHODS: We compared acute innate immune response with a viral dsRNA mimic, polyinosinic:polycytidylic acid (poly(I:C)), in brain using qRT-PCR in both C57BL/6N and C57BL/6J mice. Next, we used a neuroimmune model of escalation using poly(I:C) to compare drinking behavior between substrains. Finally, we compared brain neuroimmune response with both EtOH and repeated poly(I:C) in both substrains as a way to account for differences in EtOH behavior. RESULTS: We found that C57BL/6 substrains have differing immune response and drinking behaviors. C57BL/6N mice have a shorter but more robust inflammatory response to acute poly(I:C). In contrast, C57BL/6J mice have a smaller but longer-lasting acute immune response to poly(I:C). In our neuroimmune-induced escalation model, C57BL/6J mice but not C57BL/6N mice escalate EtOH intake after poly(I:C). Finally, only C57BL/6J mice show enhanced proinflammatory transcript abundance after poly(I:C) and EtOH, suggesting that longer-lasting immune responses are critical to neuroimmune drinking phenotypes. CONCLUSIONS: Altogether, this work has elucidated additional influences that substrain has on both innate immune response and drinking phenotypes. Our observations highlight the importance of considering and reporting the source and background used for production of transgenic and knockout mice. These data provide further evidence that genetic background must be carefully considered when investigating the role of neuroimmune signaling in EtOH abuse.
Assuntos
Consumo de Bebidas Alcoólicas/genética , Comportamento Animal , Imunidade Inata/genética , Neuroimunomodulação/genética , Consumo de Bebidas Alcoólicas/imunologia , Consumo de Bebidas Alcoólicas/fisiopatologia , Animais , Depressores do Sistema Nervoso Central/administração & dosagem , Etanol/administração & dosagem , Imunidade Inata/imunologia , Indutores de Interferon/farmacologia , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Endogâmicos , Camundongos Knockout , Camundongos Transgênicos , Modelos Animais , Neuroimunomodulação/imunologia , Poli I-C/farmacologiaAssuntos
Consumo de Bebidas Alcoólicas/imunologia , Consumo de Bebidas Alcoólicas/psicologia , Infecções por Coronavirus/prevenção & controle , Etanol/efeitos adversos , Pandemias/prevenção & controle , Pneumonia Viral/prevenção & controle , Consumo de Bebidas Alcoólicas/efeitos adversos , Betacoronavirus/efeitos dos fármacos , COVID-19 , Infecções por Coronavirus/transmissão , Etanol/farmacologia , Humanos , Pneumonia Viral/transmissão , Fatores de Proteção , SARS-CoV-2RESUMO
Alcohol consumption is a consistent protective factor for the development of autoimmune diseases such as rheumatoid arthritis (RA). The underlying mechanism for this tolerance-inducing effect of alcohol, however, is unknown. Here we show that alcohol and its metabolite acetate alter the functional state of T follicular helper (TFH) cells in vitro and in vivo, thereby exerting immune regulatory and tolerance-inducing properties. Alcohol-exposed mice have reduced Bcl6 and PD-1 expression as well as IL-21 production by TFH cells, preventing proper spatial organization of TFH cells to form TFH:B cell conjugates in germinal centers. This effect is associated with impaired autoantibody formation, and mitigates experimental autoimmune arthritis. By contrast, T cell independent immune responses and passive models of arthritis are not affected by alcohol exposure. These data clarify the immune regulatory and tolerance-inducing effect of alcohol consumption.
Assuntos
Consumo de Bebidas Alcoólicas/imunologia , Artrite Experimental/imunologia , Artrite Reumatoide/imunologia , Etanol/farmacologia , Linfócitos T Auxiliares-Indutores/efeitos dos fármacos , Ácido Acético/metabolismo , Ácido Acético/farmacologia , Animais , Artrite Experimental/prevenção & controle , Artrite Reumatoide/prevenção & controle , Autoanticorpos/imunologia , Autoimunidade/efeitos dos fármacos , Linfócitos B/efeitos dos fármacos , Linfócitos B/imunologia , Colágeno/administração & dosagem , Colágeno/imunologia , Etanol/metabolismo , Feminino , Humanos , Camundongos , Fatores de Proteção , Tolerância a Antígenos Próprios/efeitos dos fármacos , Linfócitos T Auxiliares-Indutores/imunologiaRESUMO
Murine models of chronic alcohol consumption are frequently used to investigate alcoholic liver injury and define new therapeutic targets. Lieber-DeCarli diet (LD) and Meadows-Cook diet (MC) are the most accepted models of chronic alcohol consumption. It is unclear how similar these models are at the cellular, immunologic, and transcriptome levels. We investigated the common and specific pathways of LD and MC models. Livers from LD and MC mice were subjected to histologic changes, hepatic leukocyte population, hepatic transcripts level related to leukocyte recruitment, and hepatic RNA-seq analysis. Cross-species comparison was performed using the alcoholic liver disease (ALD) transcriptomic public dataset. Despite LD mice have increased liver injury and steatosis by alcohol exposure, the number of CD45+ cells were reduced. Opposite, MC mice have an increased number of monocytes/liver by alcohol. The pattern of chemokine gradient, adhesion molecules, and cytokine transcripts is highly specific for each model, not shared with advanced human alcoholic liver disease. Moreover, hepatic RNA-seq revealed a limited and restricted number of shared genes differentially changed by alcohol exposure in these 2 models. Thus, mechanisms involved in alcohol tissue injury are model-dependent at multiple levels and raise the consideration of significant pathophysiological diversity of human alcoholic liver injury.
Assuntos
Consumo de Bebidas Alcoólicas/patologia , Alcoolismo/patologia , Hepatopatias Alcoólicas/patologia , Fígado/patologia , Consumo de Bebidas Alcoólicas/genética , Consumo de Bebidas Alcoólicas/imunologia , Alcoolismo/etiologia , Alcoolismo/genética , Alcoolismo/imunologia , Animais , Doença Crônica , Modelos Animais de Doenças , Feminino , Humanos , Fígado/imunologia , Fígado/metabolismo , Hepatopatias Alcoólicas/etiologia , Hepatopatias Alcoólicas/genética , Hepatopatias Alcoólicas/imunologia , Camundongos , Camundongos Endogâmicos C57BL , TranscriptomaRESUMO
Individuals infected with Strongyloides stercoralis have been reported to produce different immunoglobulins isotypes, yet few studies have evaluated their use in strongyloidiasis diagnosis. The aim of this work was to evaluate the immunoreactivity of different classes and subclasses of anti-S. stercoralis circulating antibodies in alcoholic patients by ELISA and to perform immunoblotting in samples with discordant results between parasitological and immunological methods. 345 male patients with a clinical diagnosis of alcoholism hospitalized at a reference center for alcoholics in Salvador, Bahia, Brazil, were included in this study. The fecal samples were examined by three different parasitological methods (spontaneous sedimentation, Baermann-Moraes and Agar Plate Culture methods). The ELISA was performed for the detection of IgG, IgG1, IgG4, IgE and IgA1 anti-S. stercoralis. Immunoblotting, for the detection of specific IgA1, was used to elucidate discordant results between parasitological and immunological methods. S. stercoralis infection frequency in alcoholic patients by parasitological methods was 21.4% (74/345). Although IgE-ELISA demonstrated a high sensitivity and specificity in non-alcoholic patients, about 30% (22/74) of alcoholics with larvae in feces were negative. IgG1-ELISA detected the lowest frequency of antibodies in alcoholic patients with larvae in feces, only 57% (42/74). IgG4-ELISA was the best assay for S. stercoralis infection immunodiagnosis. Immunoreactivity in the immunoblotting for IgA1 at 90, 75, 26 and/or 17â¯kDa bands was observed in 92% (33/36) of alcoholics with larvae excretion and negative ELISA for one or more antibody isotypes. In conclusion, IgG4-ELISA showed the highest sensitivity and specificity, thus demonstrating its superiority for strongyloidiasis immunodiagnosis in alcoholic and non-alcoholic individuals. Both, IgE and IgG1-ELISA presented high sensitivities and specificities for S. stercoralis infection diagnosis in non-alcoholics, however there was low reactivity in alcoholic individuals. This can be associated with an increased susceptibility to severe strongyloidiasis in these patients. IgA1-immunoblotting can be used to confirm S. stercoralis infection when there are discordant results between parasitological methods and ELISA.
Assuntos
Consumo de Bebidas Alcoólicas/imunologia , Alcoolismo/imunologia , Anticorpos Anti-Helmínticos/imunologia , Strongyloides stercoralis/imunologia , Estrongiloidíase/imunologia , Adulto , Idoso , Alcoolismo/parasitologia , Animais , Brasil , Ensaio de Imunoadsorção Enzimática/métodos , Fezes/parasitologia , Humanos , Imunoglobulina G/imunologia , Testes Imunológicos/métodos , Masculino , Pessoa de Meia-Idade , Projetos Piloto , Sensibilidade e Especificidade , Estrongiloidíase/diagnóstico , Estrongiloidíase/parasitologia , Adulto JovemRESUMO
Cofactors may explain why in some cases food ingestion leads to anaphylaxis while in others elicits a milder reaction or tolerance. With cofactors, reactions become more severe and/or have a lower allergen threshold. Cofactors are present in up to 58% of food anaphylaxis (FAn). Exercise, NSAIDs, and alcohol are the most frequently described, although the underlying mechanisms are poorly known. Several hypotheses have suggested the influence of these cofactors on basophils and mast cells (MCs). Exercise has been suggested to enhance MC activation by increasing plasma osmolarity, redistributing blood flow, and activating adenosine and eicosanoid metabolism. NSAIDs' cofactor effect has been related with cyclooxygenase inhibition and therefore, prostaglandin E2 (PGE2) production. Indeed, overexpression of adenosine receptor 3 (A3) gene has been described in NSAID-dependent FAn; A3 activation potentiates FcϵRI-induced MC degranulation. Finally, alcohol has been related with an increase of histamine levels by inhibition of diamino oxidase (DAO) and also with and increase of extracellular adenosine by inhibition of its uptake. However, most of these mechanisms have limited evidence, and further studies are urgently needed. In conclusion, the study of the immune-related mechanisms involved in food allergic reactions enhanced by cofactors is of the utmost interest. This knowledge will help to design both tailored treatments and prophylactic strategies that, nowadays, are non-existent.
Assuntos
Anafilaxia/imunologia , Basófilos/imunologia , Hipersensibilidade Alimentar/imunologia , Mastócitos/imunologia , Consumo de Bebidas Alcoólicas/efeitos adversos , Consumo de Bebidas Alcoólicas/imunologia , Anafilaxia/patologia , Anti-Inflamatórios não Esteroides/efeitos adversos , Anti-Inflamatórios não Esteroides/uso terapêutico , Basófilos/patologia , Degranulação Celular , Hipersensibilidade Alimentar/patologia , Humanos , Mastócitos/patologia , Receptores de IgE/imunologiaAssuntos
Consumo de Bebidas Alcoólicas/imunologia , Hipersensibilidade/imunologia , Adulto , Alérgenos/imunologia , Animais , Antígenos de Dermatophagoides/imunologia , Povo Asiático , Baratas/imunologia , Cães/imunologia , Feminino , Humanos , Imunoglobulina E/sangue , Masculino , Inquéritos Nutricionais , República da Coreia , Fatores de Risco , Caracteres SexuaisRESUMO
BACKGROUND: Rodent models of high alcohol drinking offer opportunities to better understand factors for alcohol use disorders (AUD) and test potential treatments. Selective breeding was carried out to create 2 unique High Drinking in the Dark (HDID-1, HDID-2) mouse lines that represent models of genetic risk for binge-like drinking. A number of studies have indicated that neuroimmune genes are important for regulation of alcohol drinking. We tested whether compounds shown to reduce drinking in other models also reduce alcohol intake in these unique genetic lines. METHODS: We report tests of gabapentin, tesaglitazar, fenofibrate, caffeic acid phenethyl ester (CAPE), ibrutinib, and rolipram. Although these compounds have different mechanisms of action, they have all been shown to reduce inflammatory responses. We evaluated effects of these compounds on alcohol intake. In order to facilitate comparison with previously published findings for some compounds, we employed similar schedules that were previously used for that compound. RESULTS: Gabapentin increased ethanol (EtOH) binge-like alcohol drinking in female HDID-1 and HS/NPT mice. Tesaglitazar and fenofibrate did not alter 2-bottle choice (2BC) drinking in male HDID-1 or HS/NPT mice. However, tesaglitazar had no effect on DID EtOH intake but reduced blood alcohol levels (BAL), and fenofibrate increased DID intake with no effects on BAL. CAPE had no effect on EtOH intake. Ibrutinib reduced intake in female HDID-1 in initial testing, but did not reduce intake in a second week of testing. Rolipram reduced DID intake and BALs in male and female HDID-1, HDID-2, and HS/NPT mice. CONCLUSIONS: A number of compounds shown to reduce EtOH drinking in other models, and genotypes are not effective in HDID mice or their genetically heterogeneous founders, HS/NPT. The most promising compound was the PDE4 inhibitor, rolipram. These results highlight the importance of assessing generalizability when rigorously testing compounds for therapeutic development.
Assuntos
Intoxicação Alcoólica/tratamento farmacológico , Intoxicação Alcoólica/imunologia , Sistemas de Liberação de Medicamentos/métodos , Neuroimunomodulação/imunologia , Rolipram/administração & dosagem , Consumo de Bebidas Alcoólicas/tratamento farmacológico , Consumo de Bebidas Alcoólicas/genética , Consumo de Bebidas Alcoólicas/imunologia , Intoxicação Alcoólica/genética , Alcanossulfonatos/administração & dosagem , Animais , Consumo Excessivo de Bebidas Alcoólicas/tratamento farmacológico , Consumo Excessivo de Bebidas Alcoólicas/genética , Consumo Excessivo de Bebidas Alcoólicas/imunologia , Relação Dose-Resposta a Droga , Feminino , Fenofibrato/administração & dosagem , Gabapentina/administração & dosagem , Masculino , Camundongos , Camundongos Endogâmicos , Camundongos Transgênicos , Neuroimunomodulação/efeitos dos fármacos , Fenilpropionatos/administração & dosagem , Transdução de Sinais/efeitos dos fármacos , Transdução de Sinais/fisiologiaRESUMO
This study investigated the relationship between alcohol consumption with alcohol-induced facial flushing response and rheumatoid factor (RF) in adult men. The cohort comprised 1675 men who underwent a general medical check-up between July 2016 and June 2017, including 355 non-drinkers, 498 flushers, and 822 non-flushers. One drink was defined as 14 g of alcohol. RF was considered negative if the level was less than 18 IU/mL and positive if the level was greater than 18 IU/mL. Logistic regression analyses were used. Compared to non-drinkers, the odds ratio for a positive RF among non-flushers was 0.92 (95% confidence interval [CI], 0.37-2.29) for those with an average alcohol consumption of ≤4 drinks per week, 1.64 (95% CI, 0.67-3.98) for those consuming more than 4 drinks per week but fewer than or equal to 8 drinks per week, and 1.17 (95% CI, 0.55-2.50) for those consuming more than 8 drinks per week; the differences were not statistically significant. Compared to non-drinkers, flushers also had a non-significant odds ratio for positive RF of 1.26 (95% CI, 0.54-2.90) among those with an average alcohol consumption of ≤4 drinks per week. However, flushers showed a significantly higher odds ratio for a positive RF of 3.12 (95% CI, 1.18-8.24) among those consuming more than 4 but fewer than or equal to 8 drinks per week, and 3.27 (95% CI, 1.42-7.52) among those consuming more than 8 drinks per week. Additionally, flushers consuming more than 8 drinks per week were associated with significantly higher rates of positive RF than non-flushers (odds ratio, 2.38; 95% CI, 1.05-5.17). Our study revealed that flushers consuming more than 4 drinks per week showed a higher probability of positive RF than non-drinkers. Furthermore, flushers consuming more than 8 drinks per week had a higher probability of positive RF than non-flushers. Our results strongly indicate that the average weekly alcohol consumption level and the presence or absence of flushing should be considered when interpreting the results of RF examinations in healthy men.
Assuntos
Consumo de Bebidas Alcoólicas/imunologia , Rubor/induzido quimicamente , Fator Reumatoide/imunologia , Adulto , Idoso , Estudos Transversais , Humanos , Masculino , Pessoa de Meia-Idade , Razão de Chances , Probabilidade , Estudos RetrospectivosRESUMO
BACKGROUND: Biomarkers of monocyte activation (soluble CD14 [sCD14]), inflammation (interleukin-6 [IL-6]), and altered coagulation (D-dimer) are associated with increased mortality risk in people with HIV. The objective of the Russia Alcohol Research Collaboration on HIV/AIDS (ARCH) study was to evaluate the association between heavy alcohol use and inflammatory biomarkers over time. METHODS: The study sought antiretroviral therapy naive participants with HIV (n = 350) and assessed them at baseline, 12 and 24 months. Linear mixed effects models were used to determine whether heavy drinking (self-report augmented by phosphatidylethanol [PEth], an alcohol biomarker) was longitudinally associated with IL-6, sCD14 and D-dimer adjusting for potential confounders (e.g., demographics, HIV factors, comorbid conditions). RESULTS: Participants' baseline characteristics were as follows: 71% male; mean age of 34 years; 87% self-reported hepatitis C; and 86% current smokers. Mean log10 (HIV RNA) was 4.3 copies/mL. Heavy alcohol use, based on National Institute of Alcohol Abuse and Alcoholism risky drinking criteria and PEth (versus non-heavy alcohol use) was associated with higher sCD14 (adjusted mean difference 125 ng/mL [95% CI: 42, 209]), IL-6 (ratio of means 1.35 [95% CI: 1.17, 1.55] pg/mL), and D-dimer (ratio of means 1.20 [95% CI: 1.06, 1.37] ug/mL) across the two-year follow-up. CONCLUSION: Among HIV+ adults, current heavy alcohol use is associated with higher sCD14, IL-6 and D-dimer over time. Since these biomarkers are associated with mortality, interventions to mitigate effects of heavy drinking on these immune processes merit consideration.