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Cytokines and Sickness Behavior
Author(s) -
DANTZER ROBERT,
BLUTHÉ ROSEMARIE,
LAYÉ SOPHIE,
BRETDIBAT JEANLUC,
PARNET PATRICIA,
KELLEY KEITH W.
Publication year - 1998
Publication title -
annals of the new york academy of sciences
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.712
H-Index - 248
eISSN - 1749-6632
pISSN - 0077-8923
DOI - 10.1111/j.1749-6632.1998.tb09597.x
Subject(s) - proinflammatory cytokine , vagotomy , sickness behavior , cholecystokinin , lipopolysaccharide , vagus nerve , medicine , immune system , endocrinology , peripheral , stimulation , receptor , inflammation , immunology
A bstract : 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.