Young adult binge drinkers have immunophenotypical disarrangements in peripheral natural killer cells.

Alcohol consumption is an issue of worldwide relevance and a problem of national scale in Mexico. The consumption pattern of large amounts of alcohol on the weekends is rapidly increasing in young adults between 18 and 29 years. Despite various studies that have focused on the noxious effect of alcohol in immunity, the changes in the immunoprofiles of peripheral blood cells have not been completely described. Natural killer cells (NKCs) are lymphoid-origin cells of the immune system that are responsible for defense against tumors, among other functions. In homeostatic conditions, they are found to be in a state of "dynamic balance" between activation and inhibition stimuli, which, if broken, may lead to immunosuppression or activation of cytotoxic mechanisms. In this study, we evaluated the immunoprofile of peripheral NKCs of 54 young adults, 29 of whom were binge drinkers and 25 of whom were low risk (LR), as classified by validated tools. Drinking habits were assessed. Blood samples were collected to perform hematic biometry and liver enzyme tests. Peripheral NKCs were identified by FACS, and stained for CCR2, CCR4, CCR5, CXCR4, CD69, CD127, CD137, TLR4, and Granzyme B. The data were analyzed using the t test and Mann-Whitney's U test for contrasts, and the effect size was obtained in order to evaluate the impact of each immunoprofile. The binge group showed increased expression of CCR5 and PD-1 in NKCs, respective to the LR group, and decreased expression of TLR4, along with fewer CCR4+ cells. Moreover, the increase found in CCR5 and PD-1 expression was correlated with the number of drinks in the last drinking session. Our findings show that young binge drinkers have different immunoprofiles that could suggest an early status of immunosuppression and trafficking of NKCs to the liver, which could be related to the onset of early liver damage, early in a subject's lifespan.

Activated mesenchymal stem cell administration inhibits chronic alcohol drinking and suppresses relapse-like drinking in high-alcohol drinker rats.

Neuroinflammation has been reported to follow chronic ethanol intake and may perpetuate alcohol consumption. Present studies determined the effect of human mesenchymal stem cells (hMSCs), known for their anti-inflammatory action, on chronic ethanol intake and relapse-like ethanol intake in a post-deprivation condition. Rats were allowed 12-17 weeks of chronic voluntary ethanol (10% and 20% v/v) intake, after which a single dose of activated hMSCs (5 × 105 ) was injected into a brain lateral ventricle. Control animals were administered vehicle. After assessing the effect of hMSCs on chronic ethanol intake for 1 week, animals were deprived of ethanol for 2 weeks and thereafter an ethanol re-access of 60 min was allowed to determine relapse-like intake. A single administration of activated hMSCs inhibited chronic alcohol consumption by 70% (P < 0.001), an effect seen within the first 24 hours of hMSCs administration, and reduced relapse-like drinking by 80% (P < 0.001). In the relapse-like condition, control animals attain blood ethanol ('binge-like') levels >80 mg/dl. The single hMSC administration reduced relapse-like blood ethanol levels to 20 mg/dl. Chronic ethanol intake increased by 250% (P < 0.001) the levels of reactive oxygen species in hippocampus, which were markedly reduced by hMSC administration. Astrocyte glial acidic fibrillary protein immunoreactivity, a hallmark of neuroinflammation, was increased by 60-80% (P < 0.001) by chronic ethanol intake, an effect that was fully abolished by the administration of hMSCs. This study supports the neuroinflammation-chronic ethanol intake hypothesis and suggest that mesenchymal stem cell administration may be considered in the treatment of alcohol use disorders.

Young adult binge drinkers have immunophenotypic changes in peripheral polymorphonuclear cells and monocytes.

BACKGROUND: High alcohol intake on weekends (binge drinking) is more frequent in young adults, who could undergo early liver damage. Alcohol-induced liver damage is characterized by polymorphonuclear cell (PMN) infiltration, which can be represented in the peripheral blood by altered trafficking and activation profiles. OBJECTIVE: To evaluate the PMN trafficking and activation immunophenotypic profiles in people with a binge drinking pattern. METHODS: People with binge drinking (n = 18, 8 females) or at low risk (n = 16, 13 females) based on their AUDIT and HEPCA scores were studied. Hematic biometry and liver enzyme tests were conducted. Peripheral blood leukocytes were stained for CCR5, CCR4, and CXCR4 (trafficking) and CD69 and CD127 (activation). PMNs and monocytes were analyzed by FACS. The data were analyzed using the T-test and Mann-Whitney's U-test for contrasts and principal component and Fuzzy C means analyses for clustering, with p < 0.05 considered significant. RESULTS: Compared to the low-risk group, the binge group showed higher CCR5 expression on PMNs, decreases in the CD69 percentage and positive PMNs per microliter, and decreased CXCR4 expression on monocytes. Six immunophenotypical clusters were identified, all of which were distributed following the CCR5 and CXCR4 main vectors. CONCLUSION: Young adult binge drinkers have differential PMN trafficking and activation immunophenotypes, which could be related to the initial onset of alcoholic liver disease and a systemic inflammatory state in response to their alcohol consumption pattern. These findings could lead to the future development of an early diagnostic tool.

Alterations in Activation, Cytotoxic Capacity and Trafficking Profile of Peripheral CD8 T Cells in Young Adult Binge Drinkers.

BACKGROUND: Excess of alcohol consumption is a public health problem and has documented effects on the immune system of humans and animals. Animal and in vitro studies suggest that alcohol abuse changes CD8 T cell (CD8) characteristics, however it remains unknown if the CD8 profile of binge drinkers is different in terms of activation, trafficking and cytotoxic capacity. AIM: To analyze the peripheral CD8 cytotoxic capacity, activation and trafficking phenotypic profile of Mexican young adults with regard to alcohol consumption pattern. METHODS: 55 Mexican young adults were stratified as Light (20), Intermediate (18) or Binge drinkers (17) according to their reported alcohol consumption pattern. Blood samples were obtained and hematic biometry and liver enzyme analysis were performed. Peripheral CD8 profile was established by expression of Granzyme B (GB), CD137, CD127, CD69, TLR4, PD1, CCR2, CCR4, CCR5 and CXCR4 by FACS. Data was analyzed by ANOVA, posthoc DMS and Tamhane, and principal component analysis (PCA) with varimax rotation, p<0.05. RESULTS: The Binge drinking group showed increased γGT together with increased expression of CD69 and reduced expression of TLR4, PD1, CCR2 and CXCR4 in peripheral CD8 cells. Other parameters were also specific to Binge drinkers. PCA established 3 factors associated with alcohol consumption: "Early Activation" represented by CD69 and TLR4 expression in the CD8 population; "Effector Activation" by CD69 expression in CD8 CD127(+)CD137(+) and CD8 CD25(+) CD137(+); and Trafficking by CXCR4 expression on total CD8 and CD8 GB(+)CXCR4(+), and CCR2 expression on total CD8. Binge drinking pattern showed low expression of Early Activation and Trafficking factors while Light drinking pattern exhibited high expression of Effector Activation factor. CONCLUSIONS: Alcohol consumption affects the immune phenotype of CD8 cells since binge drinking pattern was found to be associated with high CD69 and low TLR4, CXCR4 and CCR2 expression, which suggest recent activation, decreased sensitivity to LPS and lower migration capacity in response to chemokines SDF-1 and MCP-1. These results indicate that a binge-drinking pattern of alcohol consumption may induce an altered immune profile that could be related with liver damage and the increased susceptibility to infection reported to this behavior.