The DOI matches its Crossref record; 7 of the 7 references it cites were found in a registry or an index.
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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In the citing paper
“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]
In the citing paper
“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]
In the citing paper
“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]
Citations
Cites
Van Snick, J. (1990) · Annual Review of Immunology · doi:10.1146/annurev.iy.08.040190.001345 · Cited by 1,890
Biology of multifunctional cytokines: IL 6 and related molecules (IL 1 and TNF)
Akira, S., Hirano, T., Taga, T., & Kishimoto, T. (1990) · The FASEB Journal · doi:10.1096/fasebj.4.11.2199284 · Cited by 1,306
Glucocorticoids inhibit the production of IL 6 from monocytes, endothelial cells and fibroblasts
Waage, A., Slupphaug, G., & Shalaby, R. (1990) · European Journal of Immunology · doi:10.1002/eji.1830201112 · Cited by 231
Production of Interleukin-6 by Anterior Pituitary Cellsin Vitro*
Spangelo, B. L., MacLeod, R. M., & Isakson, P. C. (1990) · Endocrinology · doi:10.1210/endo-126-1-582 · Cited by 182
Nishimoto, N., Yoshizaki, K., Tagoh, H., et al. (1989) · Clinical Immunology and Immunopathology · doi:10.1016/0090-1229(89)90147-5 · Cited by 170
Tatsuno, I., Somogyvári-Vigh, A., Mizuno, K., Gottschall, P. E., Hidaka, H., & Arimura, A. (1991) · Endocrinology · doi:10.1210/endo-129-4-1797 · Cited by 145
Endotoxin-Induced Release of Interleukin-6 from Rat Medial Basal Hypothalami*
Spangelo, B. L., Judd, A. M., MacLeod, R. M., GOODMAN, D. W., & Isakson, P. C. (1990) · Endocrinology · doi:10.1210/endo-127-4-1779 · Cited by 108
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Sapolsky, R. M., Romero, L. M., & Munck, A. U. (2000) · Endocrine Reviews · doi:10.1210/edrv.21.1.0389 · Cited by 7,541
Stress-induced immune dysfunction: implications for health
Glaser, R., & Kiecolt-Glaser, J. K. (2005) · Nature Reviews Immunology · doi:10.1038/nri1571 · Cited by 2,190
Inflammation, obesity, stress and coronary heart disease: is interleukin-6 the link?
Yudkin, J. S., Kumari, M., Humphries, S. E., & Mohamed-Ali, V. (2000) · Atherosclerosis · doi:10.1016/s0021-9150(99)00463-3 · Cited by 1,775
So depression is an inflammatory disease, but where does the inflammation come from?
Berk, M., Williams, L. J., Jacka, F. N., O’Neil, A., Pasco, J. A., Moylan, S., Allen, N. B., Stuart, A. L., Hayley, A. C., Byrne, M. L., et al. (2013) · BMC Medicine · doi:10.1186/1741-7015-11-200 · Cited by 1,423
Regulation of the Hypothalamic-Pituitary-Adrenal Axis by Cytokines: Actions and Mechanisms of Action
TURNBULL, A. V., & RIVIER, C. L. (1999) · Physiological Reviews · doi:10.1152/physrev.1999.79.1.1 · Cited by 1,297
Metadata
- 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
- 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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