poly I:C treatment (Figure 3). Poly I:C treatment increased serum levels of TNFα, IL-1β, IL-6, and MCP-1 manyfold over vehicle control basal levels. Similarly brain mRNA and protein for TNFα, IL-1β, IL-6, and MCP-1 were increased manyfold by poly I:C treatment (Figures 2 and 3). Interestingly, ethanol pretreatment potentiated poly I:C responses increasing levels of proinflammatory cytokines in both blood and brain. The blood IL-1β level increased more than 10 fold in ethanol-poly I:C-treated mice (Figure 2). In brain, ethanol pretreatment potentiated poly I:C induction of TNFα mRNA from 4 to 10 fold, IL-1β mRNA from 4 to 8 fold, IL-6 mRNA from 6 to 12 fold, and MCP-1 mRNA from 28 to 49 fold (Figures 2 and 3). Ethanol pretreatment also increased poly I:C induction of TNFα, IL-1β, IL-6, and MCP-1 protein levels in brain (Figures 2 and 3). These results indicate that acute serum proinflammatory responses mimic brain proinflammatory responses. Both blood and brain show a modest ethanol response, marked poly I:C TLR3 agonist response and sequential ethanol-poly I:C amplification of proinflammatory gene induction.
