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Cited by 335Neuroinflammation and Neurodegeneration MechanismsTryptophan and brain disordersThermal Regulation in Medicine

Time course and localization patterns of interleukin-1β messenger rna expression in brain and pituitary after peripheral administration of lipopolysaccharide

Quan, N., Whiteside, M., Herkenham, M.·1998·Neuroscience
DOI 10.1016/s0306-4522(97)00350-3
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Abstract

The inflammatory cytokine interleukin-1 has been implicated as a mediator of many centrally controlled responses, such as fever and increased activity of the hypothalamic-pituitary adrenal axis, after systemic infections. To identify the neuroanatomical loci of brain interleukin-1-producing cells during infection, we investigated interleukin-1beta messenger RNA expression by in situ hybridization histochemistry using a 500 nt ribonucleotide probe applied on brain sections from rats injected intraperitoneally with 2.5 mg/kg bacterial lipopolysaccharide or saline. In control animals, interleukin-1beta messenger RNA was not detectable. In the brains of lipopolysaccharide-injected animals, two temporally and spatially distinct waves of interleukin-1beta messenger RNA induction were observed. First, cell labelling appeared at 0.5 h, peaked at 2 h, and declined at 4-8 h. The labelled cells were concentrated in circumventricular organs--organum vasculosum of the lamina terminalis, subfornical organ, median eminence, and area postrema--and in choroid plexus, meninges, and blood vessels. Second, at 8-12 h, scattered small cells became labelled throughout the entire brain parenchyma; the labelling subsided by 24 h. Labelling was not observed in any neurons. In the pituitary, lipopolysaccharide induced strong interleukin-1beta messenger RNA expression initially in the anterior lobe at 0.5-1 h, and later in the neural lobe at 1-2 h, and subsiding thereafter. The results show that at early time points, peripheral lipopolysaccharide induces interleukin-1beta message production at the blood brain barrier and in circumventricular organs where the blood brain barrier is leaky. After a time delay of 6-10 h, however, interleukin-1beta messenger RNA is primarily expressed by non-neuronal cells of the brain in the brain parenchyma. These results suggest that the source of initial brain IL-1 activity after peripheral lipopolysaccharide injection derives from cells of the blood-brain barrier and the circumventricular organs, and the sustained interleukin-1 activity in the central nervous system thereafter is derived from glia.

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  • The brain monitors peripheral innate immune responses by several parallel means, including afferent nerves, Toll-like receptors, cytokine transporters at the blood-brain barrier, and IL-1 receptors on perivascular macrophages and endothelial cells.

    “The brain monitors peripheral innate immune responses by several means that act in parallel (FIG. 1).”

    From From inflammation to sickness and depression: when the immune system subjugates the brain (2008) · cites this paper as [11]

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Authors
Quan, N., Whiteside, M., & Herkenham, M.
Affiliations
National Institutes of Health (US)
Corresponding author
Quan, N.
ORCID
Venue
Neuroscience
Publisher
Elsevier BV
Published
1998-01
Volume
83
Issue
1
Pages
281-293
ISSN
0306-4522 (ISSN-L)
DOI
10.1016/s0306-4522(97)00350-3
OpenAlex
W2013524799
Cited by
335
References
0
Citations by year
2026: 2 · 2025: 5 · 2024: 7 · 2023: 8 · 2022: 8 · 2021: 8 · 2020: 6 · 2019: 7 · 2018: 15 · 2017: 15 · 2016: 13 · 2015: 14 · 2014: 10 · 2013: 13 · 2012: 13
FWCI
10.57
Type
journal article
Language
en
Open access
closed
Licence
www.elsevier.com/tdm/userlicense/1.0/ (tdm)
Locations
  • Neuroscience (publishedVersion)
  • PubMed (publishedVersion)
Topics
  • Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
  • Life Sciences › Neuroscience › Biological Psychiatry › Tryptophan and brain disorders
  • Health Sciences › Medicine › Critical Care and Intensive Care Medicine › Thermal Regulation in Medicine
Keywords
IL-1β, lipopolysaccharide, brain mRNA expression, pituitary gland, circumventricular organs, blood-brain barrier, glial cells, neuroinflammation, infection, fever, hypothalamic-pituitary-adrenal axis, organum vasculosum of the lamina terminalis, subfornical organ, median eminence, area postrema, choroid plexus, meninges
MeSH terms
Animals, Autoradiography, Blood-Brain Barrier, Brain Chemistry, Interleukin-1, Lipopolysaccharides, Male, Pituitary Gland, RNA, Messenger, Time Factors, Rats, Sprague-Dawley, In Situ Hybridization, Rats

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