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

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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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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: www.elsevier.com/tdm/userlicense/1.0/ (tdm)
www.elsevier.com/legal/tdmrep-license (tdm)
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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Activation of the hypothalamus-pituitary-adrenal axis by bacterial endotoxins: Routes and intermediate signals

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