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1.
J Surg Res ; 244: 196-204, 2019 12.
Artigo em Inglês | MEDLINE | ID: mdl-31299436

RESUMO

BACKGROUND: Alcohol (EtOH) poses a challenge in traumatic brain injuries (TBIs) given its metabolic and neurologic impact. Studies have had opposing results regarding mortality and complication rates in the intoxicated TBI patient. We hypothesized that trauma mechanism, brain injury severity, and blood alcohol concentration (BAC) would influence the impact of EtOH on mortality in TBI. METHODS: We performed a single-institution retrospective review of consecutive adult trauma patients tested for EtOH and a diagnosis of TBI. The primary outcome was mortality, and secondary outcomes included infectious complications. The primary analysis included univariate and multivariate regression comparing mortality between intoxicated and sober patients, at different values of BAC, different brain injury severities, and among mechanisms of trauma. RESULTS: Admission EtOH was assessed in 583 patients with TBI, with 256 testing positive for EtOH and 327 testing negative. Overall, EtOH was associated with lower mortality on univariate analysis (4.7% versus 8.9%, P = 0.05) but not on multivariate analysis (P = 0.21). There was no effect of EtOH on mortality when patients were stratified by brain injury severity or among penetrating trauma victims. However, EtOH was associated with lower overall infectious complications on univariate and multivariate regression. Finally, EtOH was predictive of mortality with an area under the receiver operator characteristic curve of 0.83. CONCLUSIONS: We found that EtOH is not associated with mortality in the patient with TBI, suggesting no causative effect. However, EtOH showed some predictability of mortality based on a receiver operator characteristic analysis. Interestingly, EtOH was associated with lower infectious complications, suggesting an immunomodulatory effect of EtOH in TBI.


Assuntos
Consumo de Bebidas Alcoólicas/imunologia , Concentração Alcoólica no Sangue , Lesões Encefálicas Traumáticas/mortalidade , Etanol/imunologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Consumo de Bebidas Alcoólicas/efeitos adversos , Consumo de Bebidas Alcoólicas/sangue , Lesões Encefálicas Traumáticas/sangue , Lesões Encefálicas Traumáticas/complicações , Lesões Encefálicas Traumáticas/terapia , Infecções Relacionadas a Cateter/epidemiologia , Infecções Relacionadas a Cateter/imunologia , Etanol/sangue , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Pneumonia Associada à Ventilação Mecânica/epidemiologia , Pneumonia Associada à Ventilação Mecânica/imunologia , Estudos Retrospectivos , Sepse/epidemiologia , Sepse/imunologia , Análise de Sobrevida , Infecções Urinárias/epidemiologia , Infecções Urinárias/imunologia
3.
Addict Biol ; 23(5): 1000-1009, 2018 09.
Artigo em Inglês | MEDLINE | ID: mdl-28944558

RESUMO

The effects of acute alcohol exposure to the central nervous system are hypothesized to involve the innate immune system. The neuroimmune response to an initial and acute alcohol exposure was investigated using translocator protein 18 kDa (TSPO) PET imaging, a non-invasive marker of glial activation, in adolescent baboons. Three different alcohol-naive adolescent baboons (3-4 years old, 9 to 14 kg) underwent 18 F-DPA-714 PET experiments before, during and 7-12 months after this initial alcohol exposure (0.7-1.0 g/l). The brain distribution of 18 F-DPA-714 (VT ; in ml/cm3 ) was estimated in several brain regions using the Logan plot analysis and the metabolite-corrected arterial input function. Compared with alcohol-naive animals (VTbrain  = 3.7 ± 0.7 ml/cm3 ), the regional VT s of 18 F-DPA-714 were significantly increased during alcohol exposure (VTbrain  = 7.2 ± 0.4 ml/cm3 ; p < 0.001). Regional VT s estimated several months after alcohol exposure (VTbrain  = 5.7 ± 1.4 ml/cm3 ) were lower (p < 0.001) than those measured during alcohol exposure, but remained significantly higher (p < 0.001) than in alcohol-naive animals. The acute and long-term effects of ethanol exposure were observed globally across all brain regions. Acute alcohol exposure increased the binding of 18 F-DPA-714 to the brain in a non-human primate model of alcohol exposure that reflects the 'binge drinking' situation in adolescent individuals. The effect persisted for several months, suggesting a 'priming' of glial cell function after initial alcohol exposure.


Assuntos
Encéfalo/efeitos dos fármacos , Etanol/imunologia , Fluordesoxiglucose F18 , Neuroimunomodulação/efeitos dos fármacos , Tomografia por Emissão de Pósitrons/métodos , Pirazóis , Pirimidinas , Receptores de GABA-A/imunologia , Animais , Bebedeira/imunologia , Encéfalo/imunologia , Modelos Animais de Doenças , Etanol/farmacologia , Estudos Longitudinais , Neuroimunomodulação/imunologia , Papio , Pirazóis/imunologia , Pirimidinas/imunologia , Compostos Radiofarmacêuticos , Receptores de GABA-A/efeitos dos fármacos , Tempo
4.
Rev Med Suisse ; 13(557): 734-738, 2017 Apr 05.
Artigo em Francês | MEDLINE | ID: mdl-28722361

RESUMO

Food-dependent exercise-induced anaphylaxis (FDEIA) is a potentially severe food allergy. Physical exercise, NSAID, alcohol, infectious diseases and estrogens are recognized cofactors, able to reduce the amount of allergen needed to achieve a threshold for the induction of anaphylaxis. Various kinds of causative food but only a few responsible proteins have been identified. The best known is wheat ω5-gliadine. An oral food challenge remains the gold standard to prove the diagnosis. Its clinical application remains difficult and includes an allergen challenge, a cofactor challenge and a third step which integrates both of them in a single test. Gluten flour and NSAID + alcohol combination seem more efficient than respectively wheat flour and physical exercise in a provocation test condition.


Assuntos
Anafilaxia/diagnóstico , Exercício Físico , Hipersensibilidade Alimentar/diagnóstico , Alérgenos/imunologia , Anafilaxia/imunologia , Anti-Inflamatórios não Esteroides/imunologia , Etanol/imunologia , Hipersensibilidade Alimentar/imunologia , Glutens/imunologia , Humanos , Hipersensibilidade a Trigo/diagnóstico , Hipersensibilidade a Trigo/imunologia
5.
Sci Rep ; 7(1): 2567, 2017 05 31.
Artigo em Inglês | MEDLINE | ID: mdl-28566719

RESUMO

Chronic alcohol consumption increases the risk of hepatocellular carcinoma (HCC). However, little is known about the potential immunological mechanisms by which ethanol affects tumor progression. Here, adult male mice were administered multiple doses of diethylnitrosamine (DEN). Four and a half months later, the DEN-treated mice were placed on a liquid Lieber-DeCarli control diet or diet containing 5% ethanol for 2.5 months. At the end of the study, liver tissue samples were obtained to analyze pathology, gene expression, and hepatic mononuclear cells (MNCs). Results showed that ethanol feeding exacerbates the progression of hepatic tumors (characterized by the ratio of liver weight to body weight, and the tumor volume and diameter) in DEN-treated mice. Mechanistically, chronic alcohol consumption decreased the number of antitumor CD8+ T cells but increased the number of tumor-associated macrophages (TAMs) in the liver in DEN-initiated tumorigenesis. Besides, TAMs were prone to be M2 phenotype after alcohol consumption. Moreover, chronic alcohol consumption aggravated inflammation, fibrosis, and epithelial-mesenchymal transition (EMT) in the pathological process of HCC. These data demonstrate that chronic alcohol consumption exacerbates DEN-induced hepatocarcinogenesis by enhancing protumor immunity, impairing antitumor immunity and aggravating hepatic pathological injury. Targeting the immune system is a potential therapeutic regimen for alcohol-promoted HCC.


Assuntos
Carcinogênese/induzido quimicamente , Carcinoma Hepatocelular/imunologia , Neoplasias Hepáticas/imunologia , Fígado/efeitos dos fármacos , Consumo de Bebidas Alcoólicas/efeitos adversos , Consumo de Bebidas Alcoólicas/imunologia , Animais , Carcinogênese/patologia , Carcinoma Hepatocelular/induzido quimicamente , Carcinoma Hepatocelular/patologia , Dietilnitrosamina/imunologia , Dietilnitrosamina/toxicidade , Progressão da Doença , Etanol/imunologia , Etanol/toxicidade , Hepatócitos/efeitos dos fármacos , Hepatócitos/imunologia , Hepatócitos/patologia , Humanos , Fígado/patologia , Neoplasias Hepáticas/induzido quimicamente , Neoplasias Hepáticas/patologia , Neoplasias Hepáticas Experimentais/induzido quimicamente , Neoplasias Hepáticas Experimentais/imunologia , Neoplasias Hepáticas Experimentais/patologia , Camundongos
7.
Alcohol Clin Exp Res ; 40(11): 2260-2270, 2016 11.
Artigo em Inglês | MEDLINE | ID: mdl-27650785

RESUMO

The innate immune response in the central nervous system (CNS) participates in both synaptic plasticity and neural damage. Emerging evidence from human and animal studies supports the role of the neuroimmune system response in many actions of ethanol (EtOH) on the CNS. Research studies have shown that alcohol stimulates brain immune cells, microglia, and astrocytes, by activating innate immune receptors Toll-like receptors (TLRs) and NOD-like receptors (inflammasome NLRs) triggering signaling pathways, which culminate in the production of pro-inflammatory cytokines and chemokines that lead to neuroinflammation. This review focuses on evidence that indicates the participation of TLRs and the inflammasome NLRs signaling response in many effects of EtOH on the CNS, such as neuroinflammation associated with brain damage, cognitive and behavioral dysfunction, and adolescent brain development alterations. It also reviews findings that indicate the role of TLR4-dependent signaling immune molecules in alcohol consumption, reward, and addiction. The research data suggest that overactivation of TLR4 or NLRs increases pro-inflammatory cytokines and mediators to cause neural damage in the cerebral cortex and hippocampus, while modest TLR4 activation, along with the generation of certain cytokines and chemokines in specific brain areas (e.g., amygdala, ventral tegmental area), modulate neurotransmission, alcohol drinking, and alcohol rewards. Elimination of TLR4 and NLRP3 abolishes many neuroimmune effects of EtOH. Despite much progress being made in this area, there are some research gaps and unanswered questions that this review discusses. Finally, potential therapies that target neuroimmune pathways to treat neuropathological and behavioral consequences of alcohol abuse are also evaluated.


Assuntos
Depressores do Sistema Nervoso Central/farmacologia , Sistema Nervoso Central/efeitos dos fármacos , Etanol/farmacologia , Imunidade Inata/efeitos dos fármacos , Neuroimunomodulação/efeitos dos fármacos , Adolescente , Desenvolvimento do Adolescente , Consumo de Bebidas Alcoólicas/imunologia , Consumo de Bebidas Alcoólicas/metabolismo , Alcoolismo/metabolismo , Animais , Biomarcadores/metabolismo , Sistema Nervoso Central/metabolismo , Depressores do Sistema Nervoso Central/imunologia , Etanol/imunologia , Humanos , Proteínas NLR/metabolismo , Receptores Toll-Like/metabolismo
9.
J Anal Toxicol ; 40(2): 97-107, 2016 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-26668238

RESUMO

Urine drug screens are commonly performed to identify drug use or monitor adherence to drug therapy. The purpose of this retrospective study was to evaluate the true positive and false positive rates of one of our in-house urine drug screen panels. The urine drugs of abuse panel studied consists of screening by immunoassay then positive immunoassay results were confirmed by mass spectrometry. Reagents from Syva and Microgenics were used for the immunoassay screen. The screen was performed on a Beckman AU5810 random access automated clinical analyzer. The percent of true positives for each immunoassay was determined. Agreement with previously validated GC-MS or LC-MS-MS confirmatory methods was also evaluated. There were 8,825 de-identified screening results for each of the drugs in the panel, except for alcohol (N = 2,296). The percent of samples that screened positive were: 10.0% for amphetamine/methamphetamine/3,4-methylenedioxy-methamphetamine (MDMA), 12.8% for benzodiazepines, 43.7% for opiates (including oxycodone) and 20.3% for tetrahydrocannabinol (THC). The false positive rate for amphetamine/methamphetamine was ∼14%, ∼34% for opiates (excluding oxycodone), 25% for propoxyphene and 100% for phencyclidine and MDMA immunoassays. Based on the results from this retrospective study, the true positive rate for THC drug use among adults were similar to the rate of illicit drug use in young adults from the 2013 National Survey; however, our positivity rate for cocaine was higher than the National Survey.


Assuntos
Drogas Ilícitas/imunologia , Drogas Ilícitas/urina , Imunoensaio , Detecção do Abuso de Substâncias/métodos , Adulto , Anfetamina/imunologia , Anfetamina/urina , Cromatografia Líquida , Cocaína/imunologia , Cocaína/urina , Dronabinol/imunologia , Dronabinol/urina , Etanol/imunologia , Etanol/urina , Reações Falso-Negativas , Reações Falso-Positivas , Feminino , Cromatografia Gasosa-Espectrometria de Massas , Humanos , Masculino , Metanfetamina/imunologia , Metanfetamina/urina , Pessoa de Meia-Idade , N-Metil-3,4-Metilenodioxianfetamina/imunologia , N-Metil-3,4-Metilenodioxianfetamina/urina , Oxicodona/imunologia , Oxicodona/urina , Estudos Retrospectivos , Adulto Jovem
10.
Alcohol Res ; 35(1): 97-113, 2013.
Artigo em Inglês | MEDLINE | ID: mdl-24313169

RESUMO

Alcohol consumption alters factors that modify gene expression without changing the DNA code (i.e., epigenetic modulators) in many organ systems, including the immune system. Alcohol enhances the risk for developing several serious medical conditions related to immune system dysfunction, including acute respiratory distress syndrome (ARDS), liver cancer, and alcoholic liver disease (ALD). Binge and chronic drinking also render patients more susceptible to many infectious pathogens and advance the progression of HIV infection by weakening both innate and adaptive immunity. Epigenetic mechanisms play a pivotal role in these processes. For example, alcohol-induced epigenetic variations alter the developmental pathways of several types of immune cells (e.g., granulocytes, macrophages, and T-lymphocytes) and through these and other mechanisms promote exaggerated inflammatory responses. In addition, epigenetic mechanisms may underlie alcohol's ability to interfere with the barrier functions of the gut and respiratory systems, which also contribute to the heightened risk of infections. Better understanding of alcohol's effects on these epigenetic processes may help researchers identify new targets for the development of novel medications to prevent or ameliorate alcohol's detrimental effects on the immune system.


Assuntos
Imunidade Adaptativa/efeitos dos fármacos , Depressores do Sistema Nervoso Central/efeitos adversos , Epigênese Genética/efeitos dos fármacos , Etanol/efeitos adversos , Sistema Imunitário/efeitos dos fármacos , Imunidade Inata/efeitos dos fármacos , Imunidade Adaptativa/genética , Imunidade Adaptativa/imunologia , Depressores do Sistema Nervoso Central/imunologia , Epigênese Genética/imunologia , Etanol/imunologia , Humanos , Sistema Imunitário/imunologia , Imunidade Inata/genética , Imunidade Inata/imunologia
11.
Am J Respir Crit Care Med ; 188(6): 716-23, 2013 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-23805851

RESUMO

RATIONALE: Alcohol use disorders cause oxidative stress in the lower airways and increase susceptibility to pneumonia and lung injury. Currently, no therapeutic options exist to mitigate the pulmonary consequences of alcoholism. OBJECTIVES: We recently determined in an animal model that alcohol ingestion impairs pulmonary zinc metabolism and causes alveolar macrophage immune dysfunction. The objective of this research is to determine the effects of alcoholism on zinc bioavailability and alveolar macrophage function in human subjects. METHODS: We recruited otherwise healthy alcoholics (n = 17) and matched control subjects (n = 17) who underwent bronchoscopy for isolation of alveolar macrophages, which were analyzed for intracellular zinc, phagocytic function, and surface expression of granulocyte-macrophage colony-stimulating factor receptor; all three of these indices are decreased in experimental models. MEASUREMENTS AND MAIN RESULTS: Alcoholic subjects had normal serum zinc, but significantly decreased alveolar macrophage intracellular zinc levels (adjusted means [SE], 718 [41] vs. 948 [25] RFU/cell; P < 0.0001); bacterial phagocytosis (adjusted means [SE], 1,027 [48] vs. 1,509 [76] RFU/cell; P < 0.0001); and expression of granulocyte-macrophage colony-stimulating factor receptor ß subunit (adjusted means [SE], 1,471 [42] vs. 2,114 [35] RFU/cell; P < 0.0001]. Treating alveolar macrophages with zinc acetate and glutathione in vitro increased intracellular zinc levels and improved their phagocytic function. CONCLUSIONS: These novel clinical findings provide evidence that alcohol abuse is associated with significant zinc deficiency and immune dysfunction within the alveolar space and suggest that dietary supplementation with zinc and glutathione precursors could enhance airway innate immunity and decrease the risk for pneumonia or lung injury in these vulnerable individuals.


Assuntos
Alcoolismo/complicações , Fator Estimulador de Colônias de Granulócitos e Macrófagos/imunologia , Fator Estimulador de Colônias de Granulócitos e Macrófagos/metabolismo , Doenças do Sistema Imunitário/induzido quimicamente , Macrófagos Alveolares/metabolismo , Zinco/deficiência , Adolescente , Adulto , Alcoolismo/imunologia , Alcoolismo/metabolismo , Líquido da Lavagem Broncoalveolar/imunologia , Broncoscopia/métodos , Etanol/efeitos adversos , Etanol/imunologia , Etanol/metabolismo , Feminino , Humanos , Doenças do Sistema Imunitário/imunologia , Doenças do Sistema Imunitário/metabolismo , Imunidade Inata/efeitos dos fármacos , Imunidade Inata/imunologia , Macrófagos Alveolares/imunologia , Masculino , Pessoa de Meia-Idade , Fagocitose/efeitos dos fármacos , Fagocitose/imunologia , Adulto Jovem , Zinco/imunologia , Zinco/metabolismo
12.
Gastroenterology ; 145(2): 396-406.e1-10, 2013 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-23665276

RESUMO

BACKGROUND & AIMS: Short-chain fatty acids (SCFAs), the most abundant microbial metabolites in the intestine, activate cells via G-protein-coupled receptors (GPRs), such as GPR41 and GPR43. We studied regulation of the immune response by SCFAs and their receptors in the intestines of mice. METHODS: Inflammatory responses were induced in GPR41(-/-), GPR43(-/-), and C57BL6 (control) mice by administration of ethanol; 2, 4, 6-trinitrobenzene sulfonic-acid (TNBS); or infection with Citrobacter rodentium. We examined the effects of C rodentium infection on control mice fed SCFAs and/or given injections of antibodies that delay the immune response. We also studied the kinetics of cytokine and chemokine production, leukocyte recruitment, intestinal permeability, and T-cell responses. Primary colon epithelial cells were isolated from GPR41(-/-), GPR43(-/-), and control mice; signaling pathways regulated by SCFAs were identified using immunohistochemical, enzyme-linked immunosorbent assay, and flow cytometry analyses. RESULTS: GPR41(-/-) and GPR43(-/-) mice had reduced inflammatory responses after administration of ethanol or TNBS compared with control mice, and had a slower immune response against C rodentium infection, clearing the bacteria more slowly. SCFAs activated intestinal epithelial cells to produce chemokines and cytokines in culture and mice after administration of ethanol, TNBS, or C rodentium. These processes required GPR41 and GPR43 and were required to recruit leukocytes and activate effector T cells in the intestine. GPR41 and GPR43 activated extracellular signal-regulated kinase 1/2 and p38 mitogen-activated protein kinase signaling pathways in epithelial cells to induce production of chemokines and cytokines during immune responses. CONCLUSIONS: SCFAs activate GPR41 and GPR43 on intestinal epithelial cells, leading to mitogen-activated protein kinase signaling and rapid production of chemokines and cytokines. These pathways mediate protective immunity and tissue inflammation in mice.


Assuntos
Colite/imunologia , Células Epiteliais/imunologia , Ácidos Graxos Voláteis/imunologia , Mucosa Intestinal/citologia , Sistema de Sinalização das MAP Quinases/imunologia , Receptores Acoplados a Proteínas-G/imunologia , Animais , Citrobacter rodentium , Modelos Animais de Doenças , Infecções por Enterobacteriaceae/imunologia , Etanol/imunologia , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Receptores Acoplados a Proteínas-G/genética , Ácido Trinitrobenzenossulfônico/imunologia
13.
Alcohol ; 46(8): 783-7, 2012 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-22738858

RESUMO

On November 18, 2011, the 16th annual Alcohol and Immunology Research Interest Group (AIRIG) meeting was held at Loyola University Medical Center in Maywood, Illinois. The focus of this year's meeting was alcohol's effect on epigenetic changes and possible outcomes induced by these changes. Two sessions, which consisted of talks from invited speakers as well as presentations of selected abstracts, were held in addition to a poster session. Participants presented information on alcohol-induced alterations in histone modifications and gene expression along with immunologic responses to alcohol. Speakers shared new research specifically on histone deacetylase enzyme expression and modifications due to alcohol and the downstream effect of these modifications may have on gene expression and tissue damage. Additional studies suggested that alcohol exacerbates inflammation when combined with other insults such as infection, trauma, inhalation injury, and disease.


Assuntos
Alcoolismo/genética , Alcoolismo/imunologia , Epigênese Genética/fisiologia , Opinião Pública , Animais , Epigênese Genética/efeitos dos fármacos , Etanol/administração & dosagem , Etanol/imunologia , Humanos , Illinois , Inflamação/genética , Inflamação/imunologia
15.
Addict Biol ; 17(1): 108-20, 2012 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-21309947

RESUMO

Analysis of mouse brain gene expression, using strains that differ in alcohol consumption, provided a number of novel candidate genes that potentially regulate alcohol consumption. We selected six genes [beta-2-microglobulin (B2m), cathepsin S (Ctss), cathepsin F (Ctsf), interleukin 1 receptor antagonist (Il1rn), CD14 molecule (Cd14) and interleukin 6 (Il6)] for behavioral validation using null mutant mice. These genes are known to be important for immune responses but were not specifically linked to alcohol consumption by previous research. Null mutant mice were tested for ethanol intake in three tests: 24-hour two-bottle choice, limited access two-bottle choice and limited access to one bottle of ethanol. Ethanol consumption and preference were reduced in all the null mutant mice in the 24-hour two-bottle choice test, the test that was the basis for selection of these genes. No major differences were observed in consumption of saccharin or quinine in the null mutant mice. Deletion of B2m, Ctss, Il1rn, Cd14 and Il6 also reduced ethanol consumption in the limited access two bottle choice test for ethanol intake; with the Il1rn and Ctss null mutants showing reduced intake in all three tests (with some variation between males and females). These results provide the most compelling evidence to date that global gene expression analysis can identify novel genetic determinants of complex behavioral traits. Specifically, they suggest a novel role for neuroimmune signaling in regulation of alcohol consumption.


Assuntos
Consumo de Bebidas Alcoólicas/imunologia , Comportamento Animal , Catepsinas/genética , Proteína Antagonista do Receptor de Interleucina 1/genética , Receptores de Lipopolissacarídeos/genética , Neuroimunomodulação/genética , Microglobulina beta-2/genética , Análise de Variância , Animais , Catepsina F/genética , Catepsina F/imunologia , Catepsinas/imunologia , Depressores do Sistema Nervoso Central/administração & dosagem , Depressores do Sistema Nervoso Central/imunologia , Comportamento de Escolha , Etanol/administração & dosagem , Etanol/imunologia , Feminino , Genômica/métodos , Proteína Antagonista do Receptor de Interleucina 1/imunologia , Receptores de Lipopolissacarídeos/imunologia , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Neuroimunomodulação/imunologia , Quinina/administração & dosagem , Sacarina/administração & dosagem , Microglobulina beta-2/imunologia
16.
J Surg Res ; 173(2): 212-5, 2012 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-21737096

RESUMO

BACKGROUND: Recent evidence supports the beneficial effect of alcohol on patients with traumatic brain injury (TBI). Pneumonia is a known complication following TBI; thus, the purpose of this study was to evaluate the effects of alcohol on pneumonia rates following moderate to severe TBI. METHODS: From 2005 to 2009, the Los Angeles County Trauma Database was queried for all patients ≥ 14 y of age with isolated moderate to severe TBI and admission serum alcohol levels. The incidence of pneumonia was compared between TBI patients with and without a positive blood alcohol concentration (BAC) level. The study population was then stratified into four BAC levels: None (0 mg/dL), low (0-100 mg/dL), moderate (100-230 mg/dL), and high (≥ 230 mg/dL). Pneumonia rates were compared across these levels. RESULTS: A total of 3547 patients with isolated, moderate to severe TBI were evaluated. Nearly 66% tested positive for alcohol. The pneumonia rate was significantly lower in the TBI patients who tested positive for alcohol (2.5%) compared with those who tested negative (4.0%, P = 0.017). The pneumonia rate also decreased across increasing BAC levels (linear trend P = 0.03). After logistic regression analysis, a positive ethanol (ETOH) level was associated with a reduced incidence of pneumonia (AOR = 0.62; 95%CI: 0.41-0.93; P = 0.020). CONCLUSION: A positive serum alcohol level was associated with a significantly lower pneumonia rate in isolated, moderate to severe TBI patients. This may explain the observed mortality reduction in TBI patients who test positive for alcohol. Additional research is warranted to investigate the potential therapeutic implications of this association.


Assuntos
Consumo de Bebidas Alcoólicas/epidemiologia , Lesões Encefálicas/complicações , Depressores do Sistema Nervoso Central/imunologia , Etanol/imunologia , Pneumonia/etiologia , Adulto , Lesões Encefálicas/epidemiologia , Etanol/farmacologia , Feminino , Humanos , Imunomodulação/efeitos dos fármacos , Masculino , Pessoa de Meia-Idade , Pneumonia/epidemiologia , Estudos Retrospectivos
17.
Alcohol Clin Exp Res ; 35(8): 1435-44, 2011 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-21463338

RESUMO

BACKGROUND: Alcohol abuse has long-term deleterious effects on the immune system, and results in a depletion and loss of function of CD4(+) T lymphocytes, which regulate both innate and adaptive immunity. T-lymphocyte activation via T-cell receptor (TCR) involves the lipid raft colocalization and aggregation of proteins into the immunological signalosome, which triggers a signaling cascade resulting in the production of interleukin-2 (IL-2). IL-2 regulates the proliferation and clonal expansion of activated T cells and is essential for an effective immune response. The present work examines the mechanisms underlying ethanol-induced dysfunction of CD4(+) T lymphocytes based on the hypothesis that ethanol downregulates lipid raft-mediated TCR signal transduction and resultant IL-2 production. METHODS: Primary or cultured human T lymphocytes were exposed to ethanol for 24 hours prior to stimulation with anti-CD3/anti-CD28 antibodies or phytohemagglutinin. Effects of ethanol exposure on TCR-signaling (including activation of Lck, ZAP70, LAT, and PLCγ1) and IL-2 gene expression were examined. RESULTS: Exposure of both primary and cultured human CD4(+) T lymphocytes to physiologically relevant concentrations of ethanol leads to down-regulation of IL-2 mRNA and protein via inhibition of DNA-binding activity of NFAT, the essential transcription factor for IL-2. Ethanol decreases tyrosine phosphorylation and activation of upstream signaling proteins PLCγ1, LAT, ZAP70, and Lck. These effects are prevented by inhibition of metabolism of ethanol. Sucrose density gradient fractionation and confocal microscopy revealed that ethanol inhibited essential upstream lipid raft-mediated TCR-dependent signaling events, namely colocalization of Lck, ZAP70, LAT, and PLCγ1 with plasma membrane lipid rafts. CONCLUSIONS: Overall, our data demonstrate that ethanol inhibits lipid raft-mediated TCR-signaling in CD4(+) T lymphocytes, resulting in suppression of IL-2 production. These findings may represent a novel mechanism underlying alcohol abuse-associated immune suppression and may be particularly relevant in diseases such as HIV/AIDS and hepatitis C virus infection where alcohol abuse is a known comorbidity.


Assuntos
Depressores do Sistema Nervoso Central/efeitos adversos , Etanol/efeitos adversos , Tolerância Imunológica/efeitos dos fármacos , Interleucina-2/metabolismo , Microdomínios da Membrana/efeitos dos fármacos , Receptores de Antígenos de Linfócitos T/metabolismo , Linfócitos T CD4-Positivos/efeitos dos fármacos , Depressores do Sistema Nervoso Central/imunologia , Etanol/imunologia , Humanos , Imunoprecipitação , Interleucina-2/análise , Interleucina-2/imunologia , Células Jurkat , Microdomínios da Membrana/metabolismo , RNA Mensageiro/análise , RNA Mensageiro/biossíntese , Receptores de Antígenos de Linfócitos T/efeitos dos fármacos , Receptores de Antígenos de Linfócitos T/imunologia , Transdução de Sinais/efeitos dos fármacos , Transdução de Sinais/imunologia , Subpopulações de Linfócitos T/efeitos dos fármacos
18.
Int Arch Allergy Immunol ; 153(1): 86-94, 2010.
Artigo em Inglês | MEDLINE | ID: mdl-20357489

RESUMO

BACKGROUND: The determinants and biologic significance of IgE-mediated sensitization to cross-reactive carbohydrate determinants (CCDs) are not entirely known. An association between alcohol consumption and CCD sensitization has been reported in studies from Spain and Portugal. OBJECTIVE: To investigate the relationship of alcohol consumption with CCD sensitization, the role of alcohol dehydrogenase gene polymorphisms, and the clinical consequences of CCD sensitization. METHODS: Serum-specific IgE sensitization (> or =0.1 kU/l) to a CCD (the N-glycan from bromelain) was assessed in 1,197 adults participating in a population-based study in Copenhagen, Denmark. Alcohol consumption and atopic symptoms (rhinitis, asthma and oral allergy syndrome) were assessed by questionnaire. Examinations included skin prick tests (SPTs), qualitative multiallergen IgE test (Phadiatop), methacholine bronchial hyperreactivity, eosinophil cationic protein and alcohol dehydrogenase (ADH) gene polymorphisms. RESULTS: Alcohol consumption was significantly associated with CCD sensitization and this was particularly evident in SPT-negative individuals. The fast-metabolizing allele of the ADH1b polymorphism was significantly associated with CCD sensitization in alcohol drinkers. CCD sensitization was associated with atopic symptoms, but associations attenuated markedly when adjusting for SPT reactivity. CONCLUSIONS: Our results suggest that the positive association between alcohol consumption and CCD sensitization is universal and not specific to certain populations. The observed association between the ADH1b polymorphism and CCD sensitization may support that alcohol is causally related to the risk of CCD sensitization. The observed association between CCD sensitization and atopic phenotypes did not appear to be independent of SPT reactivity indicating limited significance of CCD sensitization per se.


Assuntos
Consumo de Bebidas Alcoólicas/imunologia , Bromelaínas/imunologia , Carboidratos/imunologia , Reações Cruzadas/imunologia , Hipersensibilidade Imediata , Imunoglobulina E/imunologia , Adolescente , Adulto , Idoso , Álcool Desidrogenase/genética , Alérgenos/imunologia , Bromelaínas/química , Carboidratos/química , Dinamarca , Etanol/imunologia , Feminino , Humanos , Hipersensibilidade Imediata/diagnóstico , Hipersensibilidade Imediata/imunologia , Hipersensibilidade Imediata/fisiopatologia , Imunoglobulina E/sangue , Masculino , Pessoa de Meia-Idade , Polimorfismo Genético , Polissacarídeos/imunologia , Adulto Jovem
19.
Alcohol Clin Exp Res ; 33(2): 220-32, 2009 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-19053973

RESUMO

BACKGROUND: Multiple line of clinical and experimental evidence demonstrates that both acute, moderate, and chronic, excessive alcohol use result in various abnormalities in the functions of the immune system. METHODS: Medline and PubMed databases were used to identify published reports with particular interest in the period of 2000-2008 in the subject of alcohol use, infection, inflammation, innate, and adaptive immunity. RESULTS: This review article summarizes recent findings relevant to acute or chronic alcohol use-induced immunomodulation and its consequences on host defense against microbial pathogens and tissue injury. Studies with in vivo and in vitro alcohol administration are both discussed. The effects of alcohol on lung infections, trauma and burn injury, liver, pancreas, and cardiovascular diseases are evaluated with respect to the role of immune cells. Specific changes in innate immune response and abnormalities in adaptive immunity caused by alcohol intake are detailed. CONCLUSION: Altered inflammatory cell and adaptive immune responses after alcohol consumption result in increased incidence and poor outcome of infections and other organ-specific immune-mediated effects.


Assuntos
Consumo de Bebidas Alcoólicas/imunologia , Depressores do Sistema Nervoso Central/imunologia , Etanol/imunologia , Sistema Imunitário/efeitos dos fármacos , Animais , Humanos , Sistema Imunitário/citologia , Sistema Imunitário/imunologia , Infecções/imunologia , Infecções/patologia , Inflamação/patologia
20.
J Immunotoxicol ; 5(1): 17-22, 2008 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-18382854

RESUMO

Drugs that target the CNS or doses of drugs near the maximum tolerated dose may cause a non-specific stress response during routine safety testing in rodents that leads to the release of corticosterone and changes immunological parameters. In situations with mild clinical signs of stress and changes to immune organs, it may be difficult to differentiate direct immunotoxicity from changes mediated by stress. To address this concern, studies were conducted to identify potential biomarker of stress in rats that could be used in routine toxicology studies. Since serial blood collections for corticosterone levels are not practical, studies were conducted to evaluate urine corticosterone and its metabolites as a potential biomarker of stress in male Sprague-Dawley rats. Exogenous corticosterone was used as a reference to identify immune system targets and determine their relative sensitivity to corticosterone. The data from rats treated with exogenous corticosterone and from rats treated with drug or chemical stressors produced linear relationships between urine corticosterone and most immunological parameters, with r-squared values greater than 0.6. Thus, quantitatively similar effects on immunological end points are produced by exogenous corticosterone and by corticosterone induced by chemical stressors with regard to their correlation to selected immunological changes. In preclinical safety testing for a new drug, the combined findings of increased urinary corticosterone and changes of the predicted magnitude and direction in blood lymphocyte and neutrophil differentials and thymus weight or cellularity would strongly suggest that the immunological effects are secondary to a drug-induced stress response. Because these results can be obtained reliably during routine preclinical evaluations, they should be useful for the weight-of-evidence approaches often used in regulatory settings.


Assuntos
Biomarcadores/urina , Corticosterona/imunologia , Corticosterona/urina , Estresse Fisiológico/imunologia , Animais , Atrazina/administração & dosagem , Atrazina/imunologia , Atrazina/toxicidade , Contagem de Células Sanguíneas , Relação Dose-Resposta a Droga , Etanol/administração & dosagem , Etanol/imunologia , Etanol/toxicidade , Masculino , Dose Máxima Tolerável , Modelos Animais , Neutrófilos/fisiologia , Ratos , Ratos Sprague-Dawley , Timo/efeitos dos fármacos , Timo/fisiologia
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