Collectively, these results strongly suggest that visfatin may be involved in inflammatory sickness responses by regulating the productions of hypothalamic pro-inflammatory cytokines and prostaglandins.
Collectively, these results suggest that visfatin is involved in a sickness response in the brain, as increased body temperature and decreased locomotor activity are representative indicators of an inflammatory sickness response.
Thus, we predicted that ME7 prion-diseased animals would show similar systemic cytokine responses but amplified CNS inflammatory and sickness behavioural responses to systemic poly I C stimulation, with respect to normal animals given the same stimulus.
Similarly, social disruption stress synergistically increased inflammatory cytokine and sickness responses to peripheral administration of LPS, IFNα or the viral analogue Poly I C in three separate studies of mice (Anisman et al., 2007; Gandhi et al., 2007; Gibb et al., 2008).
We used a similar approach recently to determine whether etoposide could induce inflammatory cytokine production and sickness behaviors when administered to mice [15].
Using this model we would expect that a clinically relevant dose of docetaxel would not induce inflammatory cytokine production or sickness behavior.
In this pathology, with increased sensitivity to pain and with sickness behavior, inflammatory cytokines could have an effect on nociception.
Similarly, in animals, exposure to a novel environment, physical restraint and foot-shock stress increase both circulating and central expression of inflammatory cytokines, and induce sickness symptoms (Dantzer et al., 2007).
Also, there is now a great deal of evidence, at least in animal models, of the role of pro-inflammatory cytokines in producing sickness behaviour that recapitulates many of the symptoms seen in patients with cancer (Illi et al, 2012).
Vagotomy attenuates this distributed neural response to peripheral inflammatory challenge and blocks corresponding sickness behaviors (34).
We have previously shown that during chronic neurodegeneration, microglia are primed by disease to produce exaggerated sickness and CNS inflammatory responses to systemic stimulation with the TLR4 agonist LPS (Combrinck et al., 2002; Cunningham et al., 2005a).
