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Cited by 277Stress Responses and CortisolNeuroinflammation and Neurodegeneration MechanismsThermal Regulation in Medicine

Activation of the hypothalamus-pituitary-adrenal axis by bacterial endotoxins: Routes and intermediate signals

Tilders, Fred J.H., DeRuk, Roel H., Van Dam, Anne-Marie, Vincent, Valerie A.M., Schotanus, Karel, Persoons, Jek H.A.·1994·Psychoneuroendocrinology
DOI 10.1016/0306-4530(94)90010-8
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Abstract

Peripheral administration of endotoxin induces brain-mediated responses, including activation of the hypothalamus-pituitary-adrenal (HPA) axis and changes in thermoregulation. This paper reviews the mechanisms by which endotoxin affects these responses. The effects on thermoregulation are complex and include macrophage-dependent hyperthermic and hypothermic responses. Low doses of endotoxin, given IP, activate peripheral macrophages to produce interleukin (IL)-1 beta, which enters the circulation and acts as a hormonal signal. IL-1 may pass fenestrated endothelium in the median eminence to stimulate corticotropin-releasing hormone (CRH) secretion from the CRH nerve-terminals. In addition, IL-1 may activate brain endothelial cells to produce IL-1, IL-6, prostaglandins, etc., and secrete these substances into the brain. By paracrine actions, these substances may affect neurons (e.g., CRH neurons) or act on microglial cells, which show IL-1-induced IL-1 production and therefore amplify and prolong the intracerebral IL-1 signal. In contrast, high doses of endotoxin given i.v. may directly stimulate endothelial cells to produce IL-1, IL-6, and prostaglandin-E2 (PGE2) and thereby activate the HPA axis in a macrophage-independent manner.

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Crossref · 10.1016/0306-4530(94)90010-8

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164 of 164 references verified0 citation errors · 0 not checkable

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  • Circulating lipopolysaccharide does not pass the blood-brain barrier to impact neurons or glial cells per se, but it modulates blood-brain barrier function by affecting tight junction proteins and brain endothelial cells to regulate immune cell trafficking and cytokine transport.

    “Finally, although circulating LPS does not pass the blood–brain barrier to impact on neurons or glial cells per se [59], LPS modulates the blood–brain barrier function by its direct effect on the tight junction proteins and thus barrier permeability, as well as its interactions with the brain endothelial cells to regulate immune cell trafficking and cytokine transport as an indirect way for gut”

    From Are the gut bacteria telling us to eat or not to eat? reviewing the role of gut microbiota in the etiology, disease progression and treatment of eating disorders (2017) · cites this paper as [59]

  • Lipopolysaccharide induces cytokine production, notably interleukin-1, interleukin-6, and tumor necrosis factor-α, from immune cells and triggers immune-endocrine-nervous changes that subsequently activate the hypothalamic-pituitary-adrenal axis.

    “By binding to its receptors on macrophages, lymphocytes, and granulocytes, LPS induces cytokine production (notably interleukin-1, interleukin-6 and tumor necrosis factor-α) from immune cells and triggers a series of changes in the immune-endocrine-nervous system that subsequently activates the HPA axis (for details please refer to a comprehensive review by Tilders and colleagues [59]).”

    From Are the gut bacteria telling us to eat or not to eat? reviewing the role of gut microbiota in the etiology, disease progression and treatment of eating disorders (2017) · cites this paper as [59]

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Authors
Tilders, F. J. H., DeRuk, R. H., Van Dam, A.-M., Vincent, V. A. M., Schotanus, K., & Persoons, J. H. A.
Affiliations
Vrije Universiteit Amsterdam (NL)
Corresponding author
Tilders, Fred J.H.
Venue
Psychoneuroendocrinology
Publisher
Elsevier BV
Published
1994
Volume
19
Issue
2
Pages
209-232
ISSN
0306-4530 (ISSN-L)
DOI
10.1016/0306-4530(94)90010-8
OpenAlex
W1989306597
Cited by
277
References
179
Citations by year
2025: 2 · 2024: 1 · 2023: 2 · 2022: 1 · 2021: 2 · 2020: 2 · 2019: 1 · 2018: 4 · 2017: 1 · 2016: 2 · 2015: 2 · 2014: 5 · 2013: 5 · 2012: 2
FWCI
3.73
Type
journal article
Language
en
Open access
closed
Licence
Locations
  • Psychoneuroendocrinology (publishedVersion)
  • PubMed (publishedVersion)
  • Pure Amsterdam UMC (submittedVersion)
  • Data Archiving and Networked Services (DANS) (submittedVersion)
Topics
  • Life Sciences › Neuroscience › Behavioral Neuroscience › Stress Responses and Cortisol
  • Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
  • Health Sciences › Medicine › Critical Care and Intensive Care Medicine › Thermal Regulation in Medicine
Keywords
hypothalamic-pituitary-adrenal axis, bacterial endotoxin, IL-1β, thermoregulation, corticotropin-releasing factor, median eminence, brain endothelial cells, microglia, prostaglandin E2, interleukin-6, macrophages, neuroendocrine signaling
MeSH terms
Adrenocorticotropic Hormone, Afferent Pathways, Animals, Corticosterone, Endothelium, Vascular, Endotoxins, General Adaptation Syndrome, Hypothalamo-Hypophyseal System, Interleukin-1, Macrophage Activation, Pituitary-Adrenal System, Dinoprostone, Signal Transduction, Interleukin-6

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