Not only ethanol but also chronic stress increases brain NF-κB activation (Koo et al. 2010; Madrigal et al. 2002), as well as the levels of cytokines, prostaglandin,4 and COX-2 (Madrigal et al. 2003), all of which have proinflammatory effects. Although acute stress–induced responses, such as elevated glucocorticoid levels, are anti-inflammatory by blocking NF-κB production, chronic elevation of glucocorticoid levels during cycles of stress and/or AOD abuse reverses these anti-inflammatory effects and indeed results in proinflammatory NF-κB activation in the frontal cortex (Munhoz et al. 2010). Thus, activation of NF-κB is a common molecular mechanism through which stress and AODs can induce innate immune genes.
