In addition to the HMGB1–TLR4 signaling cascade, multiple other proinflammatory genes are increased and have been detected postmortem in the brains of alcoholics. Initial human brain studies focused on microglia and the proinflammatory cytokine monocyte chemotactic protein-1 (MCP-1, also known as CCL2), which among the cytokines tested was induced most robustly by ethanol in brain-slice cultures (Zou and Crews 2012). Additional studies also showed increased levels of MCP-1 protein in the ventral-tegmental area, amygdala, nucleus accumbens, and hippocampus (He and Crews 2008). In addition to MCP-1, expression of the microglial marker Iba-1 also was increased. These studies indicate that neuroimmune-gene expression is increased in the human alcoholic brain.
