Stress, ethanol, other addictive drugs, as well as sensory and hormonal signals, activate an oxidation sensitive transcription factor, NF-κB (nuclear factor kappa-light-chain-enhancer of activated B cells), that is highly expressed in monocytes and microglia. Monocytes and microglia express high levels of the transcription factor NF-κB as well as low levels of innate immune genes under normal conditions. Although NF-κB is found in most cells, it is the key transcription factor involved in induction of innate immune genes in microglia and other monocyte-like cells. Stimuli such as stress, cytokines, oxidative free radicals, ultraviolet irradiation, bacterial or viral antigens, and many other signaling molecules increase NF-κB-DNA binding and transcription of many genes particularly chemokines, cytokines, oxidases and proteases (Fig. 2). We find that ethanol increases NF-κB–DNA binding in brain in-vivo (Crews et al. 2006) or in-vitro in hippocampal-entorhinal cortex (HEC) brain slice cultures (Zou and Crews 2006). Our studies and others indicate that ethanol increases transcription of NF-κB target genes including the chemokine MCP-1 (CCL2), the proinflammatory cytokines, TNFα, IL-1β, and IL6, the proinflammatory oxidases, iNOS (Zou and Crews 2010), COX (Knapp
