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Recombinant interleukin-6 activates the hypothalamic-pituitary-adrenal axis in humans.
Abstract
The inflammatory cytokines, tumor necrosis factor-alpha, interleukin-1 alpha and -beta (IL-1 alpha and -beta), and IL-6 can activate the hypothalamic-pituitary-adrenal (HPA) axis. Tumor necrosis factor-alpha and IL-1 have been tested in both experimental animals and humans, but their administration has been limited by significant toxicity, mainly severe hypotension. IL-6, on the other hand, has demonstrated modest toxicity in animals. We evaluated the ability of recombinant IL-6 to stimulate the human HPA axis in patients with cancer and a good performance status, who received daily morning sc injections of 30 micrograms/kg IL-6 for 7 consecutive days, during the course of a phase I trial. IL-6 caused impressively marked and prolonged elevations of plasma ACTH and cortisol on the first day and blunted ACTH responses on the seventh day of treatment, perhaps as a result of increased baseline cortisol levels. The overall cortisol response, however, on the seventh day was of similar magnitude, suggesting that a new equilibrium in the feedback regulation of the HPA axis occurs with chronic IL-6 administration. The toxic effects of IL-6 were modest, suggesting that it might be useful for clinical testing of the HPA axis, as an alternative to the insulin tolerance test.
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“Administration of exogenous IL-6 to rats stimulates ACTH and corticosterone production, and s.c. injection of IL-6 into human cancer patients has been shown to elevate plasma ACTH and cortisol levels (25–28).”
From Interleukin-6 is an essential, corticotropin-releasing hormone-independent stimulator of the adrenal axis during immune system activation (2000) · cites this paper as [27]
In the citing paper
“Administration of exogenous IL-6 to rats stimulates ACTH and corticosterone production, and s.c. injection of IL-6 into human cancer patients has been shown to elevate plasma ACTH and cortisol levels (25–28).”
From Interleukin-6 is an essential, corticotropin-releasing hormone-independent stimulator of the adrenal axis during immune system activation (2000) · cites this paper as [27]
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Metadata
- Authors
- Mastorakos, G., Chrousos, G. P., & Weber, J. S.
- Affiliations
- National Institutes of Health (US)
- Venue
- The Journal of Clinical Endocrinology & Metabolism
- Publisher
- The Endocrine Society
- Published
- 1993-12
- Volume
- 77
- Issue
- 6
- Pages
- 1690-1694
- ISSN
- 0021-972X (ISSN-L)
- 1945-7197
- OpenAlex
- W2048958074
- Cited by
- 591
- References
- 3
- Citations by year
- 2026: 2 · 2025: 8 · 2024: 6 · 2023: 11 · 2022: 17 · 2021: 21 · 2020: 13 · 2019: 18 · 2018: 15 · 2017: 16 · 2016: 13 · 2015: 17 · 2014: 21 · 2013: 15 · 2012: 16
- FWCI
- 10.26
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- The Journal of Clinical Endocrinology & Metabolism (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Adrenal Hormones and Disorders
- Life Sciences › Neuroscience › Behavioral Neuroscience › Stress Responses and Cortisol
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Pituitary Gland Disorders and Treatments
- Keywords
- interleukin-6, hypothalamic-pituitary-adrenal axis, ACTH, cortisol, inflammatory cytokines, TNF-α, interleukin-1, cancer patients, drug toxicity
- MeSH terms
- Adrenocorticotropic Hormone, Adult, Aged, Corticotropin-Releasing Hormone, Female, Humans, Hydrocortisone, Hypothalamo-Hypophyseal System, Male, Middle Aged, Pituitary-Adrenal System, Recombinant Proteins, Interleukin-6
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