Activation of TLR4 by LPS produces release of a number of immune mediators, including cytokines, and a “sickness” response characterized by decreased food and water intake, loss of weight, lethargy and anhedonia (Dantzer, 2001). Most of these effects of LPS are due to actions on the brain, and are generally attributed to cytokines that are released peripherally and are transported across the blood–brain barrier (Wisse et al., 2007). The increased levels of serum cytokines produced by LPS are transient (hours) and the sickness response lasts only a day or two. However, there are persistent actions of LPS exposure on brain neuroinflammatory signaling, including elevation of certain brain cytokines such as TNFα, IL-1 and CCl2 for up to 10 months (Qin et al., 2007, 2008).
