Cited by 291Stress Responses and CortisolAdrenal Hormones and DisordersTryptophan and brain disorders

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Regulation of the HPA axis by cytokines.

Turnbull, A.V., Rivier, C.·1995·Brain, Behavior, and Immunity

DOI 10.1006/brbi.1995.1026

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Abstract

Cytokines are a group of polypeptide mediators, classically associated with the regulation of immunity and inflammation. However, these peptides regulate not only local immune/inflammatory responses, but also elicit many CNS-mediated responses which accompany such immune/inflammatory reactions. This article reviews the evidence that interleukin (IL)-1, IL-6, and tumor necrosis factor alpha (TNFalpha) produce hypothalamo-pituitary-adrenal (HPA) axis activation in response to various threats to homeostasis. To aid such an examination, and to gain insights into the potential mechanisms by which these cytokines influence the HPA axis, experimental findings are discussed within a framework of criteria. If a particular cytokine plays a significant role in the regulation of the HPA axis in response to a particular pathophysiology, then necessarily: (1) receptors for that cytokine should be present within tissues associated with the HPA axis; (2) administration of that cytokine should elicit HPA activation; (3) the HPA axis should be exposed to that cytokine; and (4) inhibition of the action of that cytokine should prevent HPA activation. The evidence discussed indicates that some, if not all, of these criteria are met for each of IL-1, IL-6, and TNFalpha. However, the extensive interactions between different cytokines, the broad spectrum of pathophysiologies associated with increased cytokine production (including inflammatory and non-inflammatory stresses), and the number of tissues/cells capable of either synthesizing or responding to cytokines, suggest that multiple mechanisms mediate the influence of cytokines on the HPA axis.

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Authors: Turnbull, A. V., & Rivier, C.
Affiliations: Salk Institute for Biological Studies (US)
Venue: Brain, Behavior, and Immunity
Publisher: Elsevier BV
Published: 1995-12
Volume: 9
Issue: 4
Pages: 253-275
ISSN: 0889-1591 (ISSN-L)
DOI: 10.1006/brbi.1995.1026
OpenAlex: W1963723844
Cited by: 289
References: 0
Citations by year: 2026: 13 · 2025: 11 · 2024: 12 · 2023: 11 · 2022: 12 · 2021: 9 · 2020: 13 · 2019: 7 · 2018: 8 · 2017: 4 · 2016: 7 · 2015: 5 · 2014: 3 · 2013: 6 · 2012: 13
FWCI: 5.31
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: Brain Behavior and Immunity (publishedVersion)
PubMed (publishedVersion)
Funders: National Institute of Mental Health (MH-51774, R01MH051774)
National Institute of Diabetes and Digestive and Kidney Diseases (DK 26741, P01DK026741)
Topics: Life Sciences › Neuroscience › Behavioral Neuroscience › Stress Responses and Cortisol
Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Adrenal Hormones and Disorders
Life Sciences › Neuroscience › Biological Psychiatry › Tryptophan and brain disorders
Keywords: hypothalamic-pituitary-adrenal axis, cytokines, interleukin-1, interleukin-6, TNF-α, neuroendocrine regulation, cytokine receptors, inflammation, stress response, homeostasis
MeSH terms: Animals, Homeostasis, Humans, Hypothalamo-Hypophyseal System, Interleukin-1, Pituitary-Adrenal System, Tumor Necrosis Factor-alpha, Neuroimmunomodulation, Interleukin-6, Cytokines, Receptors, Cytokine

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Regulation of the HPA axis by cytokines.

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