Central nervous action of interleukin-1 mediates activation of limbic structures and behavioural depression in response to peripheral administration of bacterial lipopolysaccharide.
European Journal of Neuroscience. 2008-12-01; 28(12): 2499-2510
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1. Eur J Neurosci. 2008 Dec;28(12):2499-510. doi: 10.1111/j.1460-9568.2008.06549.x.
Central nervous action of interleukin-1 mediates activation of limbic structures
and behavioural depression in response to peripheral administration of bacterial
Konsman JP(1), Veeneman J, Combe C, Poole S, Luheshi GN, Dantzer R.
(1)PsychoNeuroImmunologie, Nutrition et Génétique, CNRS UMR 5526/INRA UMR 1286,
Université Victor Ségalen Bordeaux 2, Bordeaux 33076, France.
Although receptors for the pro-inflammatory cytokine interleukin-1 have long been
known to be expressed in the brain, their role in fever and behavioural
depression observed during the acute phase response (APR) to tissue infection
remains unclear. This may in part be due to the fact that interleukin-1 in the
brain is bioactive only several hours after peripheral administration of
bacterial lipopolysaccharide (LPS). To study the role of cerebral interleukin-1
action in temperature and behavioural changes, and activation of brain structures
during the APR, interleukin-1 receptor antagonist (IL-1ra; 100 microg) was
infused into the lateral brain ventricle 4 h after intraperitoneal (i.p.) LPS
injection (250 microg/kg) in rats. I.p. LPS administration induced
interleukin-1beta (IL-1beta) production in systemic circulation as well as in
brain circumventricular organs and the choroid plexus. Intracerebroventricular
(i.c.v.) infusion of IL-1ra 4 h after i.p. LPS injection attenuated the reduction
in social interaction, a cardinal sign of behavioural depression during sickness,
and c-Fos expression in the amygdala and bed nucleus of the stria terminalis.
However, LPS-induced fever, rises in plasma corticosterone, body weight loss and
c-Fos expression in the hypothalamus and caudal brainstem were not altered by
i.c.v. infusion of IL-1ra. These findings, together with our previous
observations showing that i.c.v. infused IL-1ra diffuses throughout perivascular
spaces, where macrophages express interleukin-1 receptors, can be interpreted to
suggest that circulating or locally produced brain IL-1beta acts on these cells
to bring about behavioural depression and activation of limbic structures during
the APR after peripheral LPS administration.
PMID: 19087175 [Indexed for MEDLINE]