Bi-directional immune-brain communication: Implications for understanding stress, pain, and cognition

The immune system and the central nervous system form a bi-directional communication network. The critical roles of pro-inflammatory cytokines in both the periphery and the nervous system are discussed. In the periphery, these cytokines initiate the processes that signal the brain that immune activation has occurred; and communicate this information over both neural and blood-borne routes: The arrival of these signals in the central nervous system induces a neural cascade that includes the de novo induction of pro-inflammatory cytokines. The functions of these cytokines in the nervous system are discussed, and it is argued that they play a key role in regulating the neural control of immune processes in the periphery. In addition, it is argued that these cytokines play a variety of other roles, and some implications of the cytokine network for understanding stress, behavior, sensory processing, mood, and cognition are described. The overall argument is that because brain-mediated host defense involves behavioral, sensory, mood, and cognitive alterations, immune activation, and immune products such as the cytokines can have a pervasive effect on these functions. Finally, these phenomena are placed in an evolutionary perspective. (C) 2003 Elsevier Science (USA). All rights reserved.