Trends in Neurosciences
ReviewCytokine-induced sickness behaviour: mechanisms and implications
Section snippets
Origin of peripheral cytokines
Infectious micro-organisms that invade the body encounter a first line of defence represented by tissue macrophages and liver Kupffer cells. These phagocytic cells express pattern-recognition receptors in the form of Toll-like receptors (TLRs). TLRs are defined by the presence of a conserved cytoplasmic signalling domain, the Toll–IL-1-receptor homology domain, which signals via the nuclear transcription factor NF-kB [3]. Peritoneal macrophages and Kupffer cells express TLR4, which recognizes
Role of IL-1
IL-1 is an important cytokine for the induction of sickness behaviour. Peripheral and central administration of IL-1β induces all the central components of the acute phase reaction, including fever, HPA axis activation and behavioural depression [22]. By contrast, IL-6 has only pyrogenic and corticotropic activities but no behavioural activity [23]. These findings do not imply that IL-1β is the sole cytokine that mediates sickness behaviour. In accordance with the concept of a cytokine network,
Pathophysiological implications
Based on the previous evidence, sickness behaviour can be seen as the outward expression of a reversible episode of brain inflammation that is triggered by peripheral immune stimulation. However, sickness behaviour is more than that; it has motivational properties, in the sense that it reorganizes the perception and actions of an organism in a way that depends on the environmental constraints (so as to deal the most efficiently possible with infection) [13] (Fig. 3).
Much evidence points to
Concluding remarks
Sufficient evidence is now available to accept the concept that the brain recognizes cytokines as molecular signals of sickness. Clarifying the way the brain processes information generated by the innate immune system has been accompanied by a progressive elucidation of the cellular and molecular components of the intricate system that mediates cytokine-induced sickness behaviour. However, we are still far from understanding it as a whole. Among the hundreds of genes that pro-inflammatory
Acknowledgements
It is a pleasure to record the significant contribution of our colleagues and students to the formulation of this work, In particular, we would like to thank Arnaud Aubert, Rose-Marie Bluthé, Nathalie Castanon, Jean-Luc Bret-Dibat, Lucile Capuron, Nathalie Chauvet, Keith W. Kelley, Steve Kent, Sophie Layé, Jacques Lestage, Karine Palin and Florence Pousset.
References (40)
Neural and humoral pathways of communication from the immune system to the brain: parallel or convergent?
Auton. Neurosc. Basic Clin.
(2000)Effects of the inhibition of cyclo-oxygenase 1 or 2 or 5-lipoxygenase on the activation of the hypothalamic–pituitary–adrenal axis induced by interleukin-1β in the male rat
J. Neuroendocrinol.
(2000)Cytokine-induced sickness behavior: where do we stand?
Brain Behav. Immun.
(2001)Temporal and spatial relationships between lipopolysaccharide-induced expression of Fos, interleukin-1β and inducible nitric oxide synthase in rat brain
Neuroscience
(1999)Role of IL-6 in cytokine-induced sickness behavior: a study with IL-6 deficient mice
Physiol. Behav.
(2000)Role of interleukin-1β and tumour necrosis factor-α in lipopolysaccharide-induced sickness behaviour: a study with interleukin-1 type I receptor-deficient mice
Eur. J. Neurosci.
(2000)Interleukin-1β-converting enzyme-deficient mice resist central but not systemic endotoxin-induced anorexia
Am. J. Physiol.
(1998)Blockade of brain type II interleukin-1 receptors potentiates IL1β-induced anorexia in mice
Neurosci. Lett.
(1998)Neuroimmune alterations of ENS functioning
Gut
(2000)Wasting in HIV infection and AIDS
J. Nutr.
(1999)
Cytokines and depression: fortuitous or causative association?
Mol. Psychiatry
Cytokine effects on behavior
The role of the interleukin-1/Toll-like receptor superfamily in inflammation and host defence
Microbes Infect.
Cutting edge: cell surface expression and lipopolysaccharide signaling via the toll-like receptor 4-MD-2 complex on mouse peritoneal macrophages
J. Immunol.
Kupffer cell activation by lipopolysaccharide in rats: role for lipopolysaccharide binding protein and toll-like receptor 4
Hepatology
Interleukin-1β in immune cells of the abdominal vagus nerve: a link between the immune and nervous systems?
J. Neurosci.
Activation of vagal afferents after intravenous injection of interleukin-1β: role of endogenous prostaglandins
J. Neurosci.
Involvement of cyclooxygenase-2 in LPS-induced fever and regulation of its mRNA by LPS in the rat brain
Am. J. Physiol.
Relationship of EP1–4 prostaglandin receptors with rat hypothalamic cell groups involved in lipopolysaccharide fever responses
J. Comp. Neurol.
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