Cited by 591Adrenal Hormones and DisordersStress Responses and CortisolPituitary Gland Disorders and Treatments

Recombinant interleukin-6 activates the hypothalamic-pituitary-adrenal axis in humans.

Mastorakos, G, Chrousos, G P, Weber, J S·1993·The Journal of Clinical Endocrinology & Metabolism

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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Crossref · 10.1210/jcem.77.6.8263159

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Authors
Mastorakos, G., Chrousos, G. P., & Weber, J. S.
Affiliations
National Institutes of Health (US)
Venue
The Journal of Clinical Endocrinology & Metabolism
Published
1993-12
Volume
77
Issue
6
Pages
1690-1694
ISSN
  • 0021-972X (ISSN-L)
  • 1945-7197
OpenAlex
W2048958074
Cited by
591
References
2
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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