Ethanol activated many pathways related to inflammation (Table 1, Supplementary Tables 1, 3). The NF-κB and TNFα pathways are central to inflammatory responses and alcoholic liver disease (Wang, Gao et al. 2012, Roh and Seki 2013). These pathways showed strong increases in expression of many genes, including TNFα, 15 TNF receptors or TNF associated genes, and 5 NF-κB related genes (NFKB1, NFKB2, NFKBIA or NFKBIE, IKBKE). It is notable that NFKB1 was found to be associated with risk for alcoholism (Edenberg et al., 2010). 77 genes downstream of NF-κB and 151 downstream of TNFα were affected, as were numerous genes downstream of the activated cytokines and more than 120 downstream of the interferons. The toll-like receptors are also activated by ethanol. TXNIP (thioredoxin interacting protein; 1.5-fold higher in LCL from alcoholics) is also increased 10% by ethanol treatment. TXNIP, which functionally links ER stress to the inflammasome and activation of NF-κB, was found to be 1.7 fold higher in the hippocampus of alcoholics (McClintick et al., 2013). Recently, neuroinflammation has been linked to alcoholism and may play a role in
