Subdiaphragmatic vagotomy blocks interleukin-1 beta-induced fever but doesnot reduce IL-1 beta levels in the circulation

Peripheral interleukin-1 beta has been implicated in the initiation of feve r responses, yet the pathways by which it influences brain function are sti ll unclear. Sectioning the abdominal vagus has been reported to inhibit fev er after intraperitoneal administration of interleukin-1 beta, suggesting t hat vagal afferents participate in signaling the brain to mount a fever res ponse to interleukin-1 beta. However, the inhibitory effect of subdiaphragm atic vagotomy could be due to alterations in pharmacokinetics such that the intraperitoneally injected cytokine does not reach the general circulation in sufficient quantities to activate the brain via blood-borne signaling. We measured both fever and plasma levels of interleukin-1 beta in vagotomiz ed and sham-operated rats after intraperitoneal administration of 1 mug/kg human recombinant interleukin-1 beta to determine whether vagotomy reduces fever and levels of circulating interleukin-1 beta after intraperitoneal in jection. Plasma levels of human recombinant and endogenous rat interleukin- 1 beta were measured in separate enzyme-linked immunosorbent assays. While intraperitoneal administration of human recombinant interleukin-1 beta elev ated plasma levels of this cytokine similarly in vagotomized and sham-opera ted animals, only sham-operated rats responded with fever. Plasma levels of endogenous rat interleukin-1 beta were unchanged by any treatment. These r esults demonstrate that the blockade of intraperitoneal interleukin-1 beta -induced fever after subdiaphragmatic vagotomy cannot be accounted for by a lterations of interleukin-1 beta levels in the general circulation. (C) 200 0 Elsevier Science B.V. All rights reserved.