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. We also found that microglia, the innate immune cells of brain, showed morphological activation that paralleled the level of proinflammatory gene induction across control, ethanol, poly I:C and ethanol-poly I:C groups consistent with microglia responding to blood proinflammatory signals and amplifying the responses. We show here that TNFα, IL-1β, IL-6, and MCP-1 each shows graded increases in blood that resemble graded increases in brain mRNA and protein as well as stages of microglial activation across treatment groups. Proinflammatory cytokines have a blood-to-brain saturable transport system that carries cytokines and chemokines across the blood–brain barrier into brain [41]. Increased mRNA indicates brain protein increases are likely both synthesis and transport. Microglia are the innate immune cells of brain that express cytokine and TLR receptors that respond to many immune signals including cytokines and endogenous TLR agonists, such as HMGB1, a ubiquitous protein and TLR receptor agonist [42,47,48]. Microglia are uniquely sensitive to the brain environment and are thought to initiate neuroinflammatory
