Influence of adolescent heavy session drinking on the systemic and brain innate immune system.

AIMS: The aim of the study was to evaluate rat models of intermittent alcohol abuse (heavy session/'heavy session' drinking) in relation to inflammatory changes in specific brain regions as well as in the periphery. Furthermore, the study was aimed to assess whether there are inflammatory changes in the blood of human intermittent alcohol abusers who might be associated with changes in neuronal circuitry in the brain, as assessed by functional magnetic resonance imaging (fMRI), which cause adverse effects on memory and learning. METHODS: Various regimes of intermittent alcohol administration have been used in rat models, which vary with respect to the dose and duration of ethanol administration as well as the time of abstinence. Immunohistological methods were used to identify activated microglia in specific brain regions. The response of isolated alveolar macrophages to in vitro stimuli was assessed by the assay of nitric oxide and the pro-inflammatory cytokines IL-6 and TNFα. Blood samples were collected from university students who had been heavy session drinkers for 2 years to assess whether there was an inflammatory cytokine profile that correlated with cognitive test scores as well as fMRI findings. RESULTS: The extent of microglia activation appears to depend on the doses and duration of ethanol administration. In addition, there is activation of phagocytic cells in the periphery, e.g. alveolar macrophages, in the rat models of heavy session drinking. Changes in the plasma levels of pro- and anti-inflammatory cytokines were present in heavy session drinking students, although no changes were identified in specific cognitive tests (which may be because of compensatory changes in the prefrontal cortex, as identified by fMRI). CONCLUSION: Changes in the cytokine levels induced by intermittent ethanol abuse may provoke inflammatory pathways in specific brain regions, such as hippocampus and prefrontal cortex (particularly during the stage of active neurogenesis in the adolescent brain), which might induce cognitive impairment in susceptible individuals.

Interleukin-1 alpha and beta, TNF-alpha and HTTLPR gene variants study on alcohol toxicity and detoxification outcome.

Genetic factors may influence the liability to treatment outcome and medical complications in alcoholism. In the present study we investigated the IL-1A rs1800587, IL-1B rs3087258, TNF-alpha rs1799724 and the HTTLPR variants in a sample of 64 alcohol dependents and 47 relatives versus a set of clinical parameters and outcome measures. Alcohol dependents had a less favorable clinical profile compared to relatives (higher cholesterol, triglycerides, glucose, glutamic oxaloacetic transaminase, glutamic pyruvic transaminase, gamma-glutamyltransferase). After detoxification, all clinical indexes improved and hepatic enzyme levels were similar in alcohol dependents and relatives, except for the GGT that remained significantly higher in alcohol dependents. Alcoholic depressive and anxiety scores were significantly reduced after detoxification. IL-1A, IL-1B, TNF-alpha and HTTLPR variants were not associated with any baseline clinical index or change after detoxification. In our sample IL-1A, IL-1B, TNF-alpha and HTTLPR do not appear as liability factors for alcohol toxicity or detoxification outcome, however the small sample size may influence the observed results.