Entry of Blood-Borne Cytokines into the Central Nervous System: Effects on Cognitive Processes

Blood-borne cytokines affect many aspects of the central nervous system (CNS). One of the more dramatic effects is the induction of sickness behavior. Impairments in learning and memory are an important component of sickness behavior and are largely mediated by IL-1. Many mechanisms have been proposed by which a cytokine circulating in the blood can affect functions within the CNS. We review here the role one of those mechanisms, that of transport of cytokines across the blood-brain barrier (BBB), plays in induction of the memory impairments of sickness behavior. We have shown that the posterior division of the septum (PDS) plays a key role in mediating the effects of interleukin-1α (IL-1α) on memory. Furthermore, this effect at the PDS is largely mediated by circulating IL-1α acting directly at the PDS which, in turn, depends on the ability of IL-1α to cross the BBB.