The findings summarized in this article link innate immune gene induction to addiction and alcoholism. Monocytes, microglia, and astrocytes are sensitive to AODs and stress, with repeated AOD use causing progressive innate immune gene induction that parallels changes in decision making, mood, and alcohol consumption. Stress and AODs activate NF-κB transcription in the brain, which in turn enhances expression of proinflammatory NF-κB target genes. As a result, molecules related to the innate immune response, such as the chemokine MCP-1, the proinflammatory cytokines TNFα, IL-1β, and IL-6; the proinflammatory oxidases iNOS, COX, and NOX (Qin et al. 2008); and proinflammatory proteases are found following chronic ethanol treatment. Postmortem analyses of human alcoholic brain also have demonstrated increased expression of innate immune genes, which can disrupt cognition, mood, and drug consumption and is consistent with addition-like behavior. Finally, polymorphisms of genes involved in the innate immune responses influence the risk for alcoholism. These studies suggest that innate immune genes contribute to alcoholism and may be involved in the genetic risk for alcoholism.
