likely they release cytokines into the blood. Although poly I:C-stimulated brain and blood TNFαpeaked at the same time, blood levels returned to near zero by one day, whereas brain TNFα levels remained elevated for three days, the longest time point studied. We found a single LPS injection induced a blood response of less than 24 hours, whereas the brain neuroinflammatory response lasted for more than 10 months [1], consistent with the hypothesis that increases in blood proinflammatory cytokines trigger a persistent increase in neuroinflammation. A delayed increase in liver anti-inflammatory IL-10 may contribute to loss of systemic responses, whereas brain shows a delayed decrease in IL-10, possibly contributing to persistent brain neuroinflammation [27]. In this study, we investigated TNFα, IL-1β, IL-6 and MCP-1 in both blood and brain across four treatment groups that provided graded responses increasing in magnitude, for example, low controls, small ethanol alone responses, significant poly I:C responses and the largest response from ethanol-poly I:C treatment. For example, serum MCP-1 and brain MCP-1 mRNA and protein increase in parallel from controls that are a fewfold less than ethanol alone, with poly I:C alone manyfold larger and sequential ethanol-poly I:C treatment being significantly more than any other treatments.
