We report here that intraperitoneal poly I:C when sensitized with d-GalN increased cytokines (TNFα, IL-1β, IL-6) and the cytokine-chemokine (MCP-1) in both blood and brain. Either poly I:C or d-GalN alone did not elevate serum and brain TNFα levels (data not shown), which is consistent with previous studies [4,46]. The three-day time course indicated poly I:C-induced brain and blood TNFα peaked at approximately three hours. Previously we found that intraperitoneal LPS, a toll-like receptor 4 (TLR4) agonist, increases liver, brain and blood TNFα that peaked one hour after treatment [1]. Increases in blood TNFα by TNFα injection or induced through LPS treatment required blood–brain barrier TNFα receptor-mediated transport to fully activate brain neuroinflammatory responses [1]. Many tissues may release cytokines into blood, spreading proinflammatory responses to other tissues. The liver and gut have large numbers of monocyte-like cells making it 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
