Cited by 494Stress Responses and CortisolTryptophan and brain disordersCytokine Signaling Pathways and Interactions

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Exposure to physical and psychological stressors elevates plasma interleukin 6: Relationship to the activation of hypothalamic-pituitary-adrenal axis

Zhou, D, Kusnecov, A W, Shurin, M R, DePaoli, M, Rabin, B S·1993·Endocrinology

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Abstract

Interleukin 6 (IL-6) is a pleiotropic cytokine produced by the cells of immune and nonimmune origin. Increased production of IL-6 is associated with disturbances of homeostasis, such as trauma, sepsis, or inflammatory diseases. Endotoxemia, tissue injury, or immune inflammatory reactions as well as physical or psychological stress are known to cause increased production of IL-6. We have confirmed this by showing that rats exposed to electric footshock, physical restraint, or a conditioned aversive stimulus have increased levels of plasma IL-6. Interestingly, the kinetics of the increase in plasma IL-6 resembled that of increase in plasma corticosterone. As no detectable endotoxin was found in the plasma samples from stressed and nonstressed rats and there is no evidence of tissue damage and inflammation in situations of restraint or conditioned aversive stimulus, a nonimmune origin of IL-6 is possible. Thus, the releasing of IL-6 into plasma may be under the regulation of neural and endocrine responses to stress. This hypothesis is supported by the decreased production of IL-6 in cultures of splenic cells and peripheral blood mononuclear cells from stressed animals. Furthermore, substantial attenuation of increased plasma IL-6 was achieved by adrenalectomy but not by pretreatment with the beta-receptor antagonist propranolol. The important role of the adrenal gland in the IL-6 response to stress suggests that increased plasma IL-6 may be part of the hormonal responses to stress. As IL-6 induces acute-phase proteins along with glucocorticoids from the adrenal, and regulates the secretion of various hormones from neuroendocrine and endocrine tissues, it is possible that stress-induced increase in plasma IL-6 contributes to the maintenance of homeostasis.

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Authors: Zhou, D., Kusnecov, A. W., Shurin, M. R., DePaoli, M., & Rabin, B. S.
Affiliations: University of Pittsburgh (US)
ORCID: Zhou, D
Kusnecov, A W
Shurin, M R
Venue: Endocrinology
Publisher: The Endocrine Society
Published: 1993-12
Volume: 133
Issue: 6
Pages: 2523-2530
ISSN: 0013-7227 (ISSN-L)
1945-7170
DOI: 10.1210/endo.133.6.8243274
OpenAlex: W2090877731
Cited by: 494
References: 7
Citations by year: 2026: 1 · 2025: 2 · 2024: 3 · 2023: 6 · 2022: 9 · 2021: 4 · 2020: 9 · 2019: 7 · 2018: 17 · 2017: 9 · 2016: 18 · 2015: 11 · 2014: 9 · 2013: 18 · 2012: 15
FWCI: 4.47
Type: journal article
Language: en
Open access: closed
Locations: Endocrinology (publishedVersion)
PubMed (publishedVersion)
Funders: National Institutes of Health (5r01mh043411-13)
National Institute of Mental Health (MH 43411)
Topics: Life Sciences › Neuroscience › Behavioral Neuroscience › Stress Responses and Cortisol
Life Sciences › Neuroscience › Biological Psychiatry › Tryptophan and brain disorders
Life Sciences › Immunology and Microbiology › Immunology › Cytokine Signaling Pathways and Interactions
Keywords: interleukin-6, stress, hypothalamic-pituitary-adrenal axis, corticosterone, physical restraint, adrenalectomy, propranolol, splenocytes, peripheral blood mononuclear cells, acute phase proteins, homeostasis
MeSH terms: Adrenalectomy, Adrenocorticotropic Hormone, Animals, Corticosterone, Foot, Hypothalamo-Hypophyseal System, Kinetics, Male, Pituitary-Adrenal System, Propranolol, Rats, Inbred Lew, Restraint, Physical, Stress, Physiological, Stress, Psychological, Interleukin-6, Rats

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Exposure to physical and psychological stressors elevates plasma interleukin 6: Relationship to the activation of hypothalamic-pituitary-adrenal axis

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