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Internalization and degradation of human recombinant [ 125 I]TNF-α was studied in hepatocytes isolated from rats exposed to ethanol (EtOH) either acutely (IP injection, 2.2 g kg -1 b.wt.) or chronically (14-16 weeks of EtOH feeding in liquid diet). Both acute and chronic EtOH exposure diminished cytokine binding to the cell-surface receptors. In the acute group, EtOH...
When alcohol is a large proportion of daily nutrient energy, the network of signals for energy homeostasis appears to adapt with abnormal patterns of sleep and growth hormone (GH) release along with gradual acquisition of an addictive physical dependency on alcohol. Early relapse during treatment of alcoholism is associated with a lower GH response to challenge, perhaps reflecting an altered balance...
It is well recognized that alcohol passes through the placenta and affects the fetal immune system. The underlying mechanism accounting for immune suppression is not clear. Cytokines are recognized as the principal mediators of a variety of immunologic and pathophysiologic events. The study was designed to examine whether alcohol use during pregnancy affects cytokine synthesis and secretion in the...
Patients with chronic inflammatory diseases, including Crohn's disease and rheumatoid arthritis, as well as those with certain viral infections, and patients who are transplant recipients or who have certain hematologic malignancies have been observed to have CD57 + T cell expansion in both CD4 + and CD8 + subsets. We have reported previously that alcoholic patients also have...
Ethanol is commonly used in cosmetic and pharmaceutical preparations. To test whether ethanol may cause apoptosis in skin cells, we treated A431 epidermoid skin cells and neonatal human primary skin cells with different concentrations of ethanol, for different time periods. Ethanol was toxic to cells in both a dose- and time-dependent manner and increased the percentage of cells undergoing apoptosis...
Kupffer cells play a major role in alcoholic liver disease. Oxidative stress and endotoxin are major mediators of the inflammatory process in alcoholic hepatitis. Recent evidence supports the suggestion that endotoxin-induced signal transduction begins with CD14-mediated activation of Toll-receptor 4 and subsequent activation of nuclear factor-kappa B (NF-κB) binding activity. Free radicals from reduced...
Activated monocytes and macrophages have been postulated to play an important role in the pathogenesis of alcoholic liver disease (ALD). Monocyte activation can be documented by measurement of neopterin, adhesion cell molecules, and certain proinflammatory cytokines and chemokines. We first became interested in the role of monocytes and monocyte-derived cytokines in ALD in relation to altered zinc...
Both clinical findings and results of experiments with animal models of alcoholic hepatitis have shown the importance of cytokine-mediated cell-cell interactions in the onset of ethanol-induced liver damage. Proinflammatory cytokines, such as tumor necrosis factor-alpha (TNF-α), interleukin (IL)-1beta (IL-1β), and interleukin-6, are released from Kupffer cells or infiltrating neutrophils and macrophages...
The pathogenesis of alcohol-related liver disease (ALD) remains inadequately explained. Increasing alcohol intake is associated with an increased risk of ALD, but many heavy drinkers develop no liver damage. An explanation for ALD susceptibility requires theories that extend beyond a biochemical understanding of alcohol metabolism. Several hepatic cell populations are involved in the pathogenesis...
Leukocyte infiltration in the liver is one of the most important features of alcoholic liver disease. However, in alcoholic hepatitis, the role of polymorphonuclear neutrophils (PMNs) in liver injury still remains to be fully elucidated. Furthermore, the migration of PMNs and their presence in the liver during alcoholic hepatitis have not been fully investigated. Up-regulation of chemokine secretion...
It is widely accepted that alcohol exposure is a causative factor in the occurrence of burn or other traumatic injury. It is less well known that individuals who have consumed alcohol before sustaining an injury suffer from increased morbidity and mortality compared with the morbidity and mortality of non-alcohol-consuming subjects with similar injuries. Complications due to bacterial infection are...
The pathophysiologic mechanisms underlying alcoholic chronic pancreatitis are poorly understood. Cytokines participate in the immunologic progression of acute and chronic pancreatitis and may play an important role in the development of pancreatic fibrosis. Functional polymorphisms in cytokine genes have been identified that alter cytokine production. The aims of the current investigation were to...
Sleep disturbance is one of the most prominent complaints of alcohol-dependent patients. In view of recent evidence that the immune system is integrated with other homeostatic processes ultimately regulated by the brain, the influence of sleep on host defense mechanisms and the expression of proinflammatory and T helper cell cytokines deserves attention in alcohol dependence. Although not all immune...
Astroglia are important in immunocompetence and response to injury within the CNS. Activated astroglia respond, in part, by expressing inducible nitric-oxide synthase (iNOS) and subsequent catalytic production of nitric oxide. Results from a previous study in our laboratory, in the human A172 astroglial cell line, revealed that induction of iNOS activity by tumor necrosis factor-α+interferon-γ+interleukin-1β...
In the current study, our aim was to evaluate and investigate the influence of heavy alcohol intake on serum interleukin (IL)-6, IL-8, IL-10, IL-12, and tumor necrosis factor-alpha (TNF-α) concentrations. The selection of cytokines was based on their presumptive role in the pathophysiology of alcohol dependence. On admission to the Drug-Free Substance Addiction Detoxification clinic (''ATHENA''),...
Toll-like receptors (TLRs) recognize molecular patterns associated with pathogens and initiate various mechanisms that are critical in innate resistance to infection. It has been reported that acute administration of ethanol suppresses responses mediated through TLR3 and TLR4. However, it is not known whether this is also true for other TLRs. Ligands for TLR2/TLR6 (zymosan A), TLR5 (bacterial flagellin),...
The 8th Meeting of the Alcohol and Immunology Research Interest Group (AIRIG) was held at Loyola University Medical Center, Maywood, Illinois, USA, on November 21, 2003. Reports from multiple laboratories reveal that the functional integrity of the immune system is of paramount importance to the survival of the individual after infection or injury. Evidence supports the idea that exposure to alcohol...
Acute alcohol intoxication is a frequent underlying condition associated with traumatic injury. Studies from our laboratory have been designed to examine the early hemodynamic, proinflammatory, and neuroendocrine alterations in responses to hemorrhagic shock in surgically catheterized, conscious, unrestrained, male Sprague–Dawley rats during acute alcohol intoxication (1.75-g/kg bolus, followed by...
A good deal of clinical evidence supports the idea that ethanol exposure is a causative factor in the occurrence of burn or other traumatic injury. In addition, more recent evidence reveals that individuals who sustain injury while under the influence of ethanol suffer from increased morbidity and mortality compared with those with comparable injuries who did not consume ethanol. Many of the complications...
Both dietary fatty acids and alcohol play an important role in the pathogenesis of alcoholic liver disease. Findings of studies in rats show a steatogenic role for dietary fat. A role for polyunsaturated fatty acids in alcoholic liver disease is supported by results of studies, which show that pathologic changes occur only in rats fed ethanol with polyunsaturated fatty acids. The mechanisms through...
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