Volume 840, Issue 1 p. 586-590

Cytokines and Sickness Behavior

ROBERT DANTZER

Corresponding Author

ROBERT DANTZER

Neurobiologie Intégrative, INSERM U394, Rue Camille Saint-Saens, 33077 Bordeaux Cedex, France

Address for correspondence: Dr. R. Dantzer, INSERM U394, Rue Camille Saint-Saens, 33077 Bordeaux Cedex, France; Telephone: 33 5 57 57 37 25; Fax: 33 5 56 98 90 29; e-mail: [email protected]Search for more papers by this author
ROSE-MARIE BLUTHÉ

ROSE-MARIE BLUTHÉ

Neurobiologie Intégrative, INSERM U394, Rue Camille Saint-Saens, 33077 Bordeaux Cedex, France

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SOPHIE LAYÉ

SOPHIE LAYÉ

Neurobiologie Intégrative, INSERM U394, Rue Camille Saint-Saens, 33077 Bordeaux Cedex, France

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JEAN-LUC BRET-DIBAT

JEAN-LUC BRET-DIBAT

Neurobiologie Intégrative, INSERM U394, Rue Camille Saint-Saens, 33077 Bordeaux Cedex, France

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PATRICIA PARNET

PATRICIA PARNET

Neurobiologie Intégrative, INSERM U394, Rue Camille Saint-Saens, 33077 Bordeaux Cedex, France

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KEITH W. KELLEY

KEITH W. KELLEY

Laboratory of Immunophysiology, Department of Animal Sciences, University of Illinois, Urbana, Illinois 61801

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First published: 07 February 2006
Citations: 204

Abstract

Abstract: Peripheral and central injections of interleukin-1 (IL-1) and lipopolysaccharide (LPS) induce the expression of proinflammatory cytokines in the brain and have profound depressing effects on spontaneous and learned behaviors. These effects are mediated by vagal afferents, because they are abrogated by section of the vagus nerves at the subdiaphragmatic level in rats and mice. Vagotomy does not interfere with the synthesis and release of proinflammatory cytokines at the periphery, because plasma and tissue levels of interleukin-1 of vagotomized animals are similar to those of sham-operated animals. Furthermore, the consequences of vagotomy on the host behavioral response to peripheral cytokines are specific to the intraperitoneal route of administration of cytokines because vagotomized animals are still able to respond to IL-1 injected intravenously, subcutaneously, and into the lateral ventricle of the brain. Finally, substance P and cholecystokinin do not appear to play a key role in the transmission of the immune message to the brain because pretreatment by capsaicin or by specific antagonists of CCKA and CCKB receptors does not alter the behavioral effects of LPS and IL-1. All these findings point to the role of neural afferents for transmitting the immune message from the periphery to the brain.