Exposure to physical and psychological stressors elevates plasma interleukin 6: Relationship to the activation of hypothalamic-pituitary-adrenal axis
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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Both physical and psychological stressors can provoke transient increases in proinflammatory cytokines.
“both physical and psychological stressors can provoke transient increases in proinflammatory cytokines (21, 22).”
From Chronic stress and age-related increases in the proinflammatory cytokine IL-6. (2003) · cites this paper as [22]
Interfering with HPA activation by adrenalectomy or metyrapone prevents plasma IL-6 production during stress.
“For instance, interfering with HPA activation by adrenalectomy or metyrapone (corticosterone synthesis inhibitor) prevented plasma IL-6 production during stress [15, 17].”
From Interleukin-6 Induced by Social Stress Promotes a Unique Transcriptional Signature in the Monocytes That Facilitate Anxiety (2019) · cites this paper as [15]
Rodents exposed to stressors have increased circulating IL-6.
“Parallel to clinical studies, rodents exposed to stressors (e.g., restraint, footshock and social defeat stress) have increased circulating IL-6 [14–17].”
From Interleukin-6 Induced by Social Stress Promotes a Unique Transcriptional Signature in the Monocytes That Facilitate Anxiety (2019) · cites this paper as [15]
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- Authors
- Zhou, D., Kusnecov, A. W., Shurin, M. R., DePaoli, M., & Rabin, B. S.
- Affiliations
- University of Pittsburgh (US)
- Venue
- Endocrinology
- Publisher
- The Endocrine Society
- Published
- 1993-12
- Volume
- 133
- Issue
- 6
- Pages
- 2523-2530
- ISSN
- 0013-7227 (ISSN-L)
- 1945-7170
- 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
- Health Sciences › Medicine › Oncology › 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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