interleukin-8 and Alcoholism

Recently, it was reported that there may be an activation of the inflammatory response system in detoxified alcohol-dependent patients without apparent liver disease (AWLD). The aims of the present study were to examine serum zinc (Zn) concentrations, total serum protein (TSP) and patterns obtained in the electrophoretically separated protein fractions in relation to serum interleukin-6 (IL-6) and IL-8 concentrations in detoxified AWLD patients. Zn, TSP, SP electrophoresis, and serum IL-6 and IL-8 concentrations were determined in detoxified AWLD patients and age-matched healthy volunteers. Serum Zn, TSP and the serum concentrations of albumin (Alb) and the beta fraction were significantly lower in detoxified AWLD patients than in healthy volunteers. The percentage of the alpha2 fraction was significantly higher in detoxified AWLD patients. Lower serum Zn in detoxified AWLD patients was attributable to lowered serum Alb. Lower serum Alb was significantly and negatively correlated to increased serum IL-8. The percentage of the alpha1 and alpha2 fractions were significantly and positively related to serum IL-6 and IL-8. The results show that there is an in vivo activation of the inflammatory response system in detoxified AWLD patients and that lower serum Zn may be causally related to lower serum Alb.

Topics: Adult; Alcoholism; Blood Protein Electrophoresis; Cytokines; Female; Humans; Interleukin-6; Interleukin-8; Liver Diseases, Alcoholic; Male; Serum Albumin; Zinc

Alcohol use disorder (AUD) is a highly prevalent comorbid disorder in patients with bipolar disorder (BD). Both BD and AUD were found to be associated with inflammation and cognitive deficits, but few study has been done on BD comorbid with AUD (BD+AUD). We aimed to investigate the impacts of comorbid AUD and BD on cognitive function, inflammatory and neurotrophic markers.. We recruited 641 BD patients, 150 patients with BD+AUD, and 185 healthy controls (HC). Neuropsychological tests [Wisconsin card sorting test (WCST), continuous performance test (CPT), and Wechsler memory scale - third edition (WMS-III)] and cytokine plasma levels [tumor necrosis factor-α (TNF-α), C-reactive protein (CRP), interleukin-8 (IL-8), transforming growth factor-β1 (TGF-β1), and brain-derived neurotrophic factor (BDNF)] were assessed.. BD+AUD patients had worse cognitive performance than those without AUD. There was a significant difference in the plasma levels of TNF-α, IL-8, and BDNF (P < 0.001, <0.001, and 0.01, respectively) between the patients and the HC groups. Post hoc analysis showed that BD+AUD patients had higher levels of TNF-α and IL-8 than BD-only patients (P < 0.001). Additionally, plasma IL-8 levels were negatively associated with number of completed categories in WCST (P = 0.02), and TNF-α levels were negatively associated with visual immediate index in WMS-III (P = 0.05).. Our results suggest that comorbid AUD and BD might worsen cognitive impairments and inflammatory processes. Further longitudinal studies on BD+AUD may be needed.

Topics: Alcoholism; Bipolar Disorder; Brain-Derived Neurotrophic Factor; Humans; Interleukin-8; Tumor Necrosis Factor-alpha

In the context of gut leakiness and translocation of microbial products in alcohol-associated liver disease (ALD), it is possible that systemic and liver inflammation involve the activation of circulating monocyte through gut-derived factors. We explored the association between monocytes, microbial translocation, systemic inflammation, and ALD.. Patients with alcohol use disorder following a rehabilitation program were compared with healthy controls. We determined the circulating number and proportion of monocyte subsets by FACS. The activation of signaling pathways by gut-derived microbes was analyzed by quantitative PCR in isolated monocytes. Cytokines secretion by monocytes and phagocytosis were assessed in vitro. Serum microbial translocation markers and cytokines were measured by ELISA and multiplex assay, respectively. ALD severity and liver inflammatory responses were analyzed in liver biopsies by various methods.. In patients with alcohol use disorder, the number of blood monocytes increased compared with controls. Monocytes from patients with alcohol use disorder upregulated IL-1β and IL-8 together with toll-like receptor 2 and downstream AP-1, while fungal sensor CARD9 was downregulated. IL-1β and IL-8 were actively secreted upon stimulation in vitro with the toll-like receptor 2 ligand peptidoglycan. Exposure with Escherichia coli confirmed preserved bacterial phagocytic activity. In contrast, Candida albicans stimulation leads to downregulation of IL-1β and TNFα compared with controls. Systemic cytokines and monocyte changes correlated with microbial translocation. Hepatic IL-1β and IL-8 increased with ALD severity together with liver macrophage activation and upregulation of chemokines involved in monocyte attraction.. Our results point to the contribution of activated monocytes to systemic inflammation and ALD. Monocytes likely infiltrate the liver, transform into monocyte-derived macrophages and release IL-1β and IL-8 in response to peptidoglycan and toll-like receptor 2 activation.

Topics: Alcoholism; Cytokines; Humans; Inflammation; Interleukin-8; Liver Diseases, Alcoholic; Monocytes; Peptidoglycan; Toll-Like Receptor 2

Several recent studies have pointed out the relationship of platelet size with increased mortality or adverse clinical course. Most studies show that increased mean platelet volume (MPV) may be associated with a deleterious outcome in different settings such as sepsis or neoplasia, whereas other researchers have found the opposite. In inflammatory conditions there is an altered secretion of several cytokines, some of them exerting a marked influence on platelet biogenesis and/or on platelet activation and aggregation. Alcohol use disorder is a chronic situation characterized by a protracted low-grade inflammation. In this study we analyze the relationship between proinflammatory cytokines and MPV and their relationships with mortality in patients with alcohol abuse. We determined serum levels of tumor necrosis factor (TNF)-α, interleukin (IL)-6 and IL-8 and routine laboratory variables among 184 patients with alcohol use disorder admitted to our hospital and followed-up for a median of 42 months. We found that MPV was inversely related to TNF-α (ρ=-0.34), and directly to IL-8 (ρ=0.32, p<0.001 in both cases) and to IL-6 (ρ=0.15; p = 0.046). Reduced MPV was related both with short-term (<6 months) and long-term mortality. Conclusion: These results suggest that inflammatory cytokines are strongly related to MPV. A low MPV is associated with a poor prognosis among patients with alcohol use disorder.

Topics: Alcoholism; Humans; Interleukin-8; Mean Platelet Volume; Prognosis; Retrospective Studies

The relationship between increased neuroimmune gene expression and hippocampal degeneration in alcohol use disorder (AUD) and other mental diseases is poorly understood. We report here that tumor necrosis factor receptor superfamily death receptor 3 (TNFRSF25, DR3) and Fas receptors (Fas) that initiate caspase cell death cascades are increased in AUD hippocampus and following a rat adolescent binge drinking model. Death receptors are known inducers of apoptosis and cell death that recruit death domain (DD) proteins FADD and TRADD and caspases to form death-inducing signaling complexes (DISC). In postmortem human AUD hippocampus, mRNA and IHC protein are increased for the entire death receptor cascade. In AUD hippocampus, ligand-death receptor pairs, i.e., TL1A-DR3 and FasL-Fas, were increased, as well as FADD and TRADD, and active caspase-8, -7, -9, and caspase-3. Further, pNFκB p65, a key neuroimmune transcription factor, and IL-8, a chemokine, were significantly increased. Interestingly, across AUD patients, increases in DR3 and Fas correlated with TRADD, and TRADD with active caspase+IR and IL-8+IR, consistent with coordinated activation of neuronal DISC mediated death cascades and neuroimmune gene induction in AUD. These findings support a role for DR3 and Fas neuroimmune signaling in AUD hippocampal neurodegeneration.

Topics: Alcoholism; Animals; Caspases; Cell Death; fas Receptor; Hippocampus; Humans; Interleukin-8; Rats; Receptors, Tumor Necrosis Factor

Platelet-derived growth factor (PDGF) promotes liver collagen deposition, acting on hepatic stellate cells. Despite this, low serum PDGF levels were reported in chronic hepatitis C or B infection, although some studies yield the opposite result. Since PDGF may be related not only to fibrosis but also with vascular, neuronal or muscle disease, it is important to analyze its behavior in alcoholics.. In total, 17 controls and 62 alcoholic patients consecutively admitted to the hospitalization unit of the Internal Medicine Service were included. We determined serum levels of PDGF C, routine laboratory evaluation, tumor necrosis factor-α, interleukin (IL)-6 and IL-8 and malondialdehyde (MDA) levels. We analyzed the relationships between PDGF and liver function, ethanol intake and inflammatory reaction by both univariate and multivariate analysis to discern which variables PDGF levels depend on.. Serum PDGF levels were significantly lower among patients (675 ± 466 pg/ml) than among controls (1074 ± 337 pg/ml; Z = 3.70; P < 0.001), and even lower among cirrhotics (549 ± 412 among cirrhotics vs 778 ± 487 among non-cirrhotics; Z = 2.33; P = 0.02). PDGF levels showed a direct correlation with prothrombin activity (ρ = 0.50; P < 0.001), platelet count (ρ = 0.44; P < 0.001) and inverse ones with bilirubin (ρ = -0.39; P = 0.002), IL-6 (ρ = -0.33; P = 0.016), IL-8 (ρ = -0.47; P < 0.001), and MDA levels (ρ = -0.44; P < 0.001). By multivariate analysis, only prothrombin activity and platelet count were independently related to PDGF.. PDGF-C levels are decreased in alcoholics, especially among cirrhotics. Multivariate analysis discloses that only prothrombin activity and platelet count are independently related to PDGF-C levels.

Topics: Alcohol Drinking; Alcoholism; Case-Control Studies; Female; Humans; Interleukin-6; Interleukin-8; Liver Cirrhosis, Alcoholic; Liver Function Tests; Lymphokines; Male; Malondialdehyde; Middle Aged; Platelet-Derived Growth Factor; Tumor Necrosis Factor-alpha

Obese individuals seem to be at the highest risk of contracting COVID-19 infection. Furthermore, severity of morbidity and mortality rates are higher in the developed world as compared to the developing world. One probable reason for this difference could be the difference in living conditions and exposure to other infections. Secondly, the difference in food especially, alcohol use may have deteriorating effects superimposed with obesity. Our hypothesis suggests that a combination of alcohol consumption and obesity causes low immunity and makes the individual prone to develop 'cytokine storm' and 'acute respiratory distress syndrome'; the hallmark of COVID-19 mortality and morbidity. Thus, we propose that reducing any one trigger can have a beneficial effect in combating the disease severity.

Topics: Adipose Tissue; Alcohol Drinking; Alcoholism; Angiotensin-Converting Enzyme 2; China; COVID-19; Cytokines; Humans; Immune System; Inflammation; Interleukin-8; Obesity; Treatment Outcome; Tumor Necrosis Factor-alpha

Cannabis use is increasing due to recent legislative changes. In addition, cannabis is often used in conjunction with alcohol. The airway epithelium is the first line of defense against infectious microbes. Toll-like receptors (TLR) recognize airborne microbes and initiate the inflammatory cytokine response. The mechanism by which cannabis use in conjunction with alcohol affects pulmonary innate immunity mediated by TLRs is unknown.. Samples and data from an existing cohort of individuals with alcohol use disorders (AUDs), along with samples from additional participants with cannabis use alone and with AUD were utilized. Subjects were categorized into the following groups: no alcohol use disorder (AUD) or cannabis use (control) (n = 46), AUD only (n = 29), cannabis use-only (n = 39), and AUD and cannabis use (n = 29). The participants underwent bronchoscopy with bronchoalveolar lavage (BAL) and airway epithelial brushings. We measured IL-6, IL-8, TNF⍺, and IL-10 levels in BAL fluid, and performed real-time PCR for TLR1-9 on the airway epithelial brushings.. We found significant increases in TLR2 with AUD alone, cannabis use alone, and cannabis use with AUD, compared to control. TLR5 was increased in cannabis users compared to control, TLR6 was increased in cannabis users and cannabis users with AUD compared to control, TLR7 was increased in cannabis users compared to control, and TLR9 was increased in cannabis users compared to control. In terms of cytokine production, IL-6 was increased in cannabis users compared to control. IL-8 and IL-10 were increased in AUD only.. AUD and cannabis use have complex effects on pulmonary innate immunity that promote airway inflammation.

Topics: Adult; Alcoholism; Bronchoalveolar Lavage Fluid; Case-Control Studies; Female; Humans; Immunity, Innate; Interleukin-10; Interleukin-6; Interleukin-8; Lung; Male; Marijuana Abuse; Middle Aged; Real-Time Polymerase Chain Reaction; Toll-Like Receptors; Tumor Necrosis Factor-alpha; Young Adult

This study examined the effects of chronic alcohol consumption in the rat erythrocytes membrane as well as the involvement of reactive oxygen species and proinflammatory cytokines in its pathogenicity in rats and evaluated the ameliorating effects of myrtle berries seeds aqueous extract (MBSAE).. Fifty adult male Wistar rats were equally divided into five groups and treated daily for two months as follows: control, ethanol (3 g kg. Exposure of rats to alcohol caused significant changes of some haematological parameters, enhanced erythrocytes hemolysis as well as an overproduction of reactive oxygen species such as H. MBSAE possess active compounds, which exert marked protective effects in chronic alcohol intoxication, possibly by regulating the erythrocytes osmotic stability as well as antioxidant and inflammatory mediators.

Topics: Alcoholism; Animals; Antioxidants; Erythrocytes; Ethanol; Gene Expression Regulation; Glutathione; Hemolysis; Hydrogen Peroxide; Hydroxyl Radical; Interleukin-1beta; Interleukin-6; Interleukin-8; Lipid Peroxidation; Male; Myrtus; Plant Extracts; Rats; Rats, Wistar; Seeds; Superoxides; Tumor Necrosis Factor-alpha

Alcoholics are known to have more severe airway diseases of the lung, such as bronchitis. Little is known about why this phenomenon is observed. We hypothesized that alcohol may modulate Toll-like receptor 2 (TLR2), which regulates inflammation caused by gram-positive bacteria.. Airway epithelial cells [primary bronchial epithelial cells (NHBE) and 16HBE 14o-] were exposed to 0 to 100 mM alcohol for 0 to 24 hours. Real time PCR was used to quantify TLR2 mRNA. Protein levels of TLR2 were determined using Western blots and fluorescence activated cell sorting (FACS) on cells exposed to 0, 50, and 100 mM alcohol. Finally, cells were "primed" with alcohol, stimulated with a TLR2 agonist (peptidoglycan), and interleukin 8 (IL-8) release was measured.. Alcohol, at biologically relevant concentrations (25 to 100 mM), caused a 2 to 3-fold time- and concentration-dependent increase in TLR2 mRNA in normal human bronchial epithelial cells and 16HBE 14o- cells. Western blots for TLR2 revealed a qualitative increase in TLR2 protein in cells exposed to 100 mM alcohol. FACS showed that TLR2 was quantitatively increased on the surface of airway epithelial cells that were exposed to alcohol. Airway cells that were primed with alcohol produced nearly twice as much IL-8 in response to 40 ng of peptidoglycan than naive cells.. Alcohol upregulates TLR2 message and protein in the airway epithelium. This leads to exaggerated inflammation in response to environmental stimuli that would normally be well tolerated in airway epithelial cells. This may be a partial explanation of why alcoholics have more severe airway disease than nonalcoholics.

Topics: Alcoholism; Bronchi; Bronchitis; Cells, Cultured; Central Nervous System Depressants; Dose-Response Relationship, Drug; Epithelial Cells; Ethanol; Humans; Interleukin-8; Peptidoglycan; RNA, Messenger; Time Factors; Toll-Like Receptor 2; Up-Regulation

Preliminary data suggest that polymorphisms in cytokine genes may be involved in the genetic predisposition to alcoholic liver cirrhosis or alcohol use disorders. We thus analyze the association between these diseases and the following polymorphisms: -33T>C IL4, -174 G>C IL6, -251 T>A IL8 and 1188 A>C IL12B.. 258 male alcoholics (161 without liver disease and 97 with liver cirrhosis) and 101 healthy controls were genotyped for the above mentioned polymorphisms. We examined the relationship between genotype and allele frequencies and the presence of disease, as well as the correlation with combinations of putative pro-inflammatory genotypes. Haplotypes were inferred using the expectation-maximization algorithm and haplotype frequencies were compared.. We found no statistically significant association between any of these polymorphisms or the combinations of pro-inflammatory polymorphisms and the risk of alcoholic liver cirrhosis or alcohol abuse or dependence. Haplotype analysis of the IL4 and IL12B polymorphisms did not show any statistical relationship either.. Our results do not support the hypothesis that the analyzed polymorphisms confer differences in alcoholic liver cirrhosis or alcohol use disorders susceptibility.

Topics: Adult; Aged; Aged, 80 and over; Alcoholism; Gene Frequency; Genetic Predisposition to Disease; Humans; Interleukin-12; Interleukin-4; Interleukin-6; Interleukin-8; Liver Cirrhosis, Alcoholic; Male; Middle Aged; Polymorphism, Genetic

Chronic alcoholic patients have a threefold to fourfold increased risk for developing a severe infection or septic shock after surgery, which might be due to altered immune response. The aim of this outcome matched study was to investigate proinflammatory and anti-inflammatory immune parameters during the course of infection and subsequent septic shock in chronic alcoholic patients, and to compare these parameters with those in nonalcoholic patients.. Twenty-eight patients from a cohort of fifty-six with either pneumonia or peritonitis and subsequent septic shock were selected. Fourteen patients were chronic alcoholics whereas fourteen were nonalcoholic patients. Chronic alcoholic patients met criteria (Diagnostic and Statistical Manual of Mental Disorders IV, of the American Psychiatric Association) for alcohol abuse or dependence. Measurements were performed during the onset of infection (within 24 hours after the onset of infection), in early septic shock (within 12 hours after onset of septic shock) and in late septic shock (72 hours after the onset). Blood measurements included proinflammatory and anti-inflammatory cytokines.. Chronic alcoholic patients exhibited significantly lower plasma levels of IL-8 (P < 0.010) during the onset of infection than did matched nonalcoholic patients. In early septic shock, chronic alcoholic patients had significantly decreased levels of IL-1beta (P < 0.015), IL-6 (P < 0.016) and IL-8 (P < 0.010). The anti-inflammatory parameters IL-10 and tumour necrosis factor receptors I and II did not differ between alcoholic and nonalcoholic patients.. At the onset of infection and during early septic shock, chronic alcoholic patients had lower levels of proinflammatory immune parameters than did nonalcoholic patients. Therefore, immunomodulatory therapy administered early may be considered in chronic alcoholic patients at the onset of an infection because of their altered proinflammatory immune response.

Topics: Adult; Aged; Alcoholism; Case-Control Studies; Chronic Disease; Humans; Interleukin-1; Interleukin-10; Interleukin-8; Middle Aged; Peritonitis; Pneumonia; Predictive Value of Tests; Receptors, Tumor Necrosis Factor; Risk Factors; Shock, Septic; Tumor Necrosis Factor-alpha

The aims of the present study were to examine (1) the inflammatory response system (IRS), through measurements of serum interleukin-6 (IL-6), soluble IL-6 receptor (sIL-6R), sgp130 (the soluble form of the IL-6 transducer signal protein), CC16 (Clara Cell protein; an endogenous anti-cytokine), IL-1R antagonist (IL-1RA), IL-8 and sCD14; and (2) the availability of plasma total tryptophan to the brain in chronic alcoholic patients without apparent liver disease (AWLD). Detoxified AWLD patients had significantly lower plasma tryptophan and serum CC16 and significantly higher serum IL-1RA and IL-8 concentrations than normal volunteers. There were significant correlations between the availability of tryptophan to the brain and serum IL-6, IL-8 and IL-1RA (all negative) and CC16 (positive). The results suggest that (1) there is, in detoxified AWLD patients, an activation of the monocytic arm of cell-mediated immunity and a lowered anti-inflammatory capacity of the serum; and that (2) lower availability of plasma tryptophan to the brain in detoxified AWLD patients is related to activation of the IRS. Lower CC16 may be one factor predisposing chronic alcoholic patients toward infectious disorders.

Topics: Adult; Alcoholism; Antigens, CD; Cytokine Receptor gp130; Female; Humans; Inflammation; Interleukin 1 Receptor Antagonist Protein; Interleukin-6; Interleukin-8; Lipopolysaccharide Receptors; Male; Membrane Glycoproteins; Proteins; Receptors, Interleukin-6; Serotonin; Sialoglycoproteins; Tryptophan; Uteroglobin

Chronic alcohol intoxication has been associated with increased migration of inflammatory leukocytes to the liver that may contribute to the development of alcoholic hepatitis in susceptible individuals. Thus, this work was performed to examine the mechanism by which neutrophils [polymorphonuclear neutrophils (PMNS)] are sequestered in the liver during prolonged consumption of alcohol. Male Sprague-Dawley rats were fed with Sustacal supplemented by 36% alcohol, or isocaloric diet for 16 weeks. Circulating blood PMNs were collected and examined for CD18 (beta 2-integrin) adhesion molecule expression. Monoclonal antibody 1F12, an anti-CD18 antibody and potent neutropenic agent, was used to detect CD18 on PMNs. More than 97% of neutrophils obtained from pair and ethanol-fed rats were positive for the antibody. Fluorescence intensity of fluorescein isothiocyanate-1F12 binding to PMNs from ethanol-fed rat was significantly enhanced 2-fold compared with the pair-fed controls. The release of chemoattractant and free radical-generating activity in culture supernatants of Kupffer cells was also examined. Twenty-four hr culture supernatants of Kupffer cells from chronic alcoholic rats enhanced the migration and superoxide anion generation by normal PMNs, compared with those of the pair-fed rats. Antirat interleukin-8 antiserum inhibited chemotactic activity and superoxide generating capacity of culture supernatants. These results suggest that upregulation of adhesion molecules on PMNs and chemotactic factor release from Kupffer cells may contribute, at least in part, to enhanced migration of inflammatory leukocytes to the liver during chronic alcohol intoxication.

Topics: Alcoholic Intoxication; Alcoholism; Animals; CD18 Antigens; Chemotactic Factors; Chemotaxis, Leukocyte; Hepatitis, Alcoholic; Interleukin-8; Kupffer Cells; Liver; Male; Neutrophils; Rats; Rats, Sprague-Dawley; Superoxides; Up-Regulation

Chronic alcohol consumption has been associated with suppression of a number of immune parameters. This study was designed to investigate the relationship between chronic alcohol ingestion and cessation with respect to release of interleukin-6 (IL-6) and interleukin-8 (IL-8) using highly specific and sensitive ELISA assays, as well as a functional assay, natural killer cell cytotoxic activity. ELISAs were developed to determine the amount of IL-6 and IL-8 release by peripheral blood mononuclear cells (PBMCs). Two groups of subjects were recruited: young (18-22 years old), nonalcoholic users (controls) and long-term alcoholics (35-55 years old). Blood samples were collected at time 0 from all subjects and from alcoholics 28 days after treatment had begun and alcohol use had ceased. Then mitogen-stimulated release of cytokines by peripheral blood cells was determined. The abstaining controls, and the alcoholics, after 30 days of abstinence, tended to produce lower amounts of IL-6 and IL-8, although these differences were not statistically significant. Natural killer cell activity was not statistically different between the young groups, yet appeared to increase once alcohol use discontinued. Some of the cells from the controls (abstainers) were incubated with ethanol (EtOH). Its content in sealed wells was measured after the time of incubation of PBMCs. When EtOH was serially diluted in plates, some well-well diffusion was noted, but the maximum concentration of EtOH never fell below 0.3% from an initial concentration of 0.5%, and at no time was the EtOH concentration gradient completely lost, even after 66 hr of incubation.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Adolescent; Adult; Alcohol Drinking; Alcohol Withdrawal Delirium; Alcoholism; Enzyme-Linked Immunosorbent Assay; Humans; Interleukin-6; Interleukin-8; Killer Cells, Natural; Liver Diseases, Alcoholic; Male; Monocytes