**2.6. Activation of multiple neuroimmune genes in human alcoholic brains**

In human brain-slice cultures, multiple ethanol-induced cytokines are released. Among all, monocyte chemotactic protein-1 (MCP-1) showed increased levels in the amygdala, nucleus accumbens, VAT and hippocampus [66]. In alcoholic brains, elevated levels of TLR 2, TLR3, TLR4 and HMGB1 (high-mobility group box 1) were found in the orbital frontal cortex (OTC) [67]. Release of HMGB1 leads to disruption of synaptic plasticity which causes hyperexcitability of neurotransmitters due to ethanol exposure. There is an increased level of IL-1β inflammatory marker in an alcoholic brain (hippocampus) causing neuro-degeneration [68]. RAGE (HMGB1 receptor) has shown an increased level in an alcoholic brain [69].
