Several animal studies suggest that chronic alcohol intake alters CNS immune and inflammatory responses through interference with NF-κB and expression of NF-κB-controlled genes [61]–[64]. Thus, chronic alcohol administration up-regulates inflammatory mediators in the animal brain and isolated astrocytes followed by activation of NF-κB and the upregulation of inducible NO synthase and cyclooxygenase-2 expression [61], [62]. Neuroinflammation may be also promoted by serum TNFα and other cytokines elevated due to systemic and hepatic inflammation induced by alcohol drinking [63]. Serum cytokines apparently enter the brain where they activate microglia. Serum and brain-produced TNFα acting through the NF-κB system may inhibit glutamate transport and, consequently, induce a hyperglutamatergic state that contributes to increased drinking and neurodegeneration [63].
