Volume 856, Issue 1 p. 132-138

Molecular Basis of Sickness Behaviora

ROBERT DANTZER

Corresponding Author

ROBERT DANTZER

Neurobiologie intégrative, INSERM U394, Rue Camille Saint-Saens, 33077 Bordeaux Cédex, France

Address for correspondence: Dr. R. Dantzer, INSERM U394, Rue Camille Saint-Saens, 33077 Bordeaux Cédex, France. Phone, 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 Cédex, France

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GILLES GHEUSI

GILLES GHEUSI

Neurobiologie intégrative, INSERM U394, Rue Camille Saint-Saens, 33077 Bordeaux Cédex, France

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SANDRINE CREMONA

SANDRINE CREMONA

Neurobiologie intégrative, INSERM U394, Rue Camille Saint-Saens, 33077 Bordeaux Cédex, France

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SOPHIE LAYÉ

SOPHIE LAYÉ

Neurobiologie intégrative, INSERM U394, Rue Camille Saint-Saens, 33077 Bordeaux Cédex, France

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PATRICIA PARNET

PATRICIA PARNET

Neurobiologie intégrative, INSERM U394, Rue Camille Saint-Saens, 33077 Bordeaux Cédex, France

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KEITH W. KELLEY

KEITH W. KELLEY

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

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First published: 07 February 2006
Citations: 187
a

This work was supported by INRA, INSERM, DRET, Commission of the European Communities (CT 97-2492 and 97-0149), and the National Institutes of Health (Grants MH-51569 and DK-49311 to K.W.K.).

Abstract

ABSTRACT: Peripheral and central injections of lipopolysaccharide (LPS), a cytokine inducer, and recombinant proinflammatory cytokines such as interleukin-1β (IL-1β) induce sickness behavior in the form of reduced food intake and decreased social activities. Mechanisms of the behavioral effects of cytokines have been the subject of much investigation during the last 3 years. At the behavioral level, the profound depressing effects of cytokines on behavior are the expression of a highly organized motivational state. At the molecular level, sickness behavior is mediated by an inducible brain cytokine compartment that is activated by peripheral cytokines via neural afferent pathways. Centrally produced cytokines act on brain cytokine receptors that are similar to those characterized on peripheral immune and nonimmune cells, as demonstrated by pharmacologic experiments using cytokine receptor antagonists, neutralizing antibodies to specific subtypes of cytokine receptors, and gene targeting techniques. Evidence exists that different components of sickness behavior are mediated by different cytokines and that the relative importance of these cytokines is not the same in the peripheral and central cytokine compartments.