The interplay between brain, behavior, and immune responses in the etiology and progression of alcohol abuse is a paradigm-shifting direction in addiction research that has transformed therapeutic outlook for alcohol use disorders (AUDs). Alcohol is thought to increase neuroimmune-related gene and protein expression through (i) gut-derived microbial products that activate innate immune cells, causing systemic induction of proinflammatory cytokines that are transported from blood to brain, as well as (ii) direct actions in the brain, where cross talk among neurons, glia, and other cells contributes to the release and signaling of immune molecules with inflammatory and neuromodulatory properties (Crews and Vetreno, 2016).

Interest in the alcohol-neuroimmune field was fueled by gene expression studies showing strong representation of immune- and inflammatory-related genes in brains from human alcoholics and rodents exposed to chronic alcohol (Liu et al, 2006; Robinson et al, 2014). Deletion of chemokines and other immune genes reduced alcohol drinking in mice and provided corroborating behavioral validation for several immune mediators that were predicted by the genomic studies (Blednov et al, 2012; Robinson et al, 2014). In contrast, immune activation by lipopolysaccharide (LPS) produced prolonged increases in alcohol consumption in mice, and treatment with either LPS or chronic intermittent alcohol produced overlapping changes in mouse brain transcriptomes (Robinson et al, 2014). The LPS-induced escalation in drinking may be related to persistent activation of immune genes in the brain that are also induced by chronic alcohol exposure.

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