THERMOGENIC AND CORTICOSTERONE RESPONSES TO INTRAVENOUS CYTOKINES (IL-1-BETA AND TNF-ALPHA) ARE ATTENUATED BY SUBDIAPHRAGMATIC VAGOTOMY

The brain orchestrates changes in behavior and physiology as a consequ ence of peripheral immune activation and infection. These changes requ ire that the brain receives signals from the periphery that an immunol ogical challenge has occurred. Previous research has established thar cytokines play a role in signalling the brain. What remains unclear, h owever, is how peripheral cytokines signal the central nervous system, A recent proposal is that cytokines signal the brain by stimulating p eripheral nerves. The hypothesis slates that following infection and t he release of cytokines such as IL-1 beta into local tissue or microva sculature, IL-1 beta stimulates IL-1 receptors on vagal afferent termi nals, or more likely on cells of vagal paraganglia. Vagal afferents, i n turn, signal the brain. Previous work has demonstrated that transect ion of the vagus below the level of the diaphragm blocks or attenuates many illness consequences of intraperitoneally (i.p.) administered li popolysaccharide (LPS) or IL-1 beta. The present studies extend these findings by examining the effect of subdiaphragmatic vagotomy on illne ss consequences following intravenously (i.v.) administered IL-1 beta and TNF-alpha. Subdiaphragmatic vagotomy attenuated both the fever res ponse and corticosterone response produced by i.v, administered cytoki nes, This effect was dose dependent. The results add support to the hy pothesis that vagal afferents are involved in peripheral cytokine-lo-b rain communication. (C) 1998 Elsevier Science B.V. All rights reserved .