title: The mechanisms of immune-to-brain communication in inflammation as a drug target.
abstract: There is considerable evidence that the peripheral immune system can signal the brain to elicit a sickness response during infection and inflammation. The induction of the sickness response involves the expression of proinflammatory cytokines such as interleukin (IL)-1beta, tumor necrosis factor-alpha (TNF-alpha), and IL-6, both in the periphery and in the brain. The mechanisms by which peripheral cytokines can affect brain function have been the subject of much debate. The precise mechanisms by which cytokines signal the central nervous system (CNS) are unknown, but possibilities include: 1) the direct entry of cytokine into the brain across the blood-brain barrier by a saturable transport mechanism: 2) the interaction of cytokine with circumventricular organs such as the orgnum vasculosum of the lamina terminalis [OVLT] and area postrema, which lack the blood-brain barrier; and 3) activation of afferent neurons of the vagus nerve. Increasing evidence has suggested that the afferent vagus nerve is an important pathway for immune-to-brain communication. However, there are inconsistent findings for the involvement of the afferent vagus nerve in the mediation of transmitting inflammatory signals to the brain. Thus, we describe here the functional relevance of the vagal afferent nerve in mediating these effects. An understanding of the mechanisms involved in immune-to-brain communication should permit us to create new drugs as therapeutic targets to decrease sickness or promote recovery. This review focuses on recent discoveries of the multipathway mechanisms for the induction of sickness behavior mediated through neuroimmune interactions in the CNS.
authors.affiliation: Department of Pharmacology, Graduate School of Pharmaceutical Sciences, Hokkaido University, Sapporo 060-0812, Japan. hosoi@pharm.hokudai.ac.jp
authors.forename: Toru
authors.initials: T
authors.lastname: Hosoi
authors.forename: Yasunobu
authors.initials: Y
authors.lastname: Okuma
authors.forename: Yasuyuki
authors.initials: Y
authors.lastname: Nomura
mesh_terms: D001921:Brain / Q000187:drug effects / Q000503:physiopathology*; D016207:Cytokines / Q000502:physiology; D016503:Drug Delivery Systems; D006801:Humans; D007107:Immune System / Q000187:drug effects / Q000503:physiopathology*; D007249:Inflammation / Q000503:physiopathology*; D009474:Neurons / Q000502:physiology; D015398:Signal Transduction / Q000502:physiology
chemical_list: D016207:Cytokines