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Cited by 95Thyroid Disorders and TreatmentsAdrenal Hormones and DisordersGrowth Hormone and Insulin-like Growth Factors

Acute and delayed effects of a single-dose injection of interleukin-6 on thyroid function in healthy humans

Torpy, D.J., Tsigos, C., Lotsikas, A.J., Defensor, R., Chrousos, G.P., Papanicolaou, D.A.·1998·Metabolism
DOI 10.1016/s0026-0495(98)90338-9
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Abstract

Interleukin-6 (IL-6) is produced in response to inflammatory and noninflammatory stress and acts as the principal regulator of the acute-phase protein response. IL-6 stimulates the hypothalamic-pituitary-adrenal axis and may be involved in the thyroid function abnormalities observed in nonthyroidal illness (NTI). This study examined the effects of single-dose IL-6 (3 microg/kg subcutaneously [s.c.]) in healthy human subjects: 19 received IL-6 and 13 received control saline injection. The dose of IL-6 was chosen on the basis of previous studies indicating that the peak IL-6 level after injection reaches concentrations observed with major stress such as abdominal surgery. Plasma levels of thyrotropin (TSH), free thyroxine (FT4), total T4, 3,5-3'-L-triiodothyronine (T3), 3,3'-5'-L-triiodothyronine or reverse T3 (rT3), and thyroxine-binding globulin (TBG) were measured over a 4-hour period and 24 hours after IL-6 injection. Plasma TSH levels were 27% lower 240 minutes after IL-6 relative to control levels (0.93 +/- 0.10 v 1.28 +/- 0.18 mIU/mL, P = .001), but recovered by 24 hours. Plasma FT4 was elevated at 240 minutes compared with the controls (1.16 +/- 0.04 v 1.03 +/- 0.03 ng/dL, P = .0002). T4 levels were also elevated at 240 minutes (7.8 +/- 0.36 v 7.05 +/- 0.37 microg/dL, P = .0003). TBG levels were not significantly changed at this time point. At 24 hours, T3 levels were 19% lower than the control values (87.6 +/- 5.1 v 108.5 +/- 5.4 ng/dL, P = .0002); plasma rT3 levels were elevated by 21% compared with control levels (30.6 +/- 1.7 v 24.3 +/- 1.3 ng/dL, P = .002), while FT4 levels returned to normal. The changes in T3/rT3 levels were reminiscent of the pattern observed in NTI that may be due to inhibition of type-1 5'-deiodinase. Cortisol levels were greatly elevated after IL-6 compared with control values; peak levels were observed 120 minutes after IL-6 injection (28.7 +/- 1.6 v 9.5 +/- 1.0 ng/dL, P < .0001). This elevation in cortisol may have contributed to the suppression of TSH levels and inhibition of type-1 5'-deiodinase activity. Alternatively, IL-6 may have suppressed TSH secretion via a direct suprapituitary action. The elevation of T4 and FT4 levels may have been due to inhibition of T4 degradation at the liver and/or by direct action of IL-6 on the thyroid gland. These findings demonstrate the potent effects of IL-6 on thyroid hormone metabolism in healthy individuals, and suggest that IL-6 may act directly or indirectly at two or more sites on thyroid hormone secretion and metabolism.

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Crossref · 10.1016/s0026-0495(98)90338-9

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  • After injection of IL-6 into healthy volunteers, T4 and free T4 increased after 4 hours but T3 levels were reduced 24 hours later, indicating a rapid downregulation of T3 by IL-6.

    “After injection of IL-6 into healthy volunteers, T4 and free T4 increased after 4 hours but T3 levels were reduced 24 hours later, which indicates a rapid downregulation of this biologically active hormone by IL-6 [132].”

    From Interaction of the endocrine system with inflammation: a function of energy and volume regulation (2014) · cites this paper as [132]

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Authors
Torpy, D. J., Tsigos, C., Lotsikas, A. J., Defensor, R., Chrousos, G. P., & Papanicolaou, D. A.
Affiliations
National Institutes of Health (US)
ORCID
Venue
Metabolism
Publisher
Elsevier BV
Published
1998-10
Volume
47
Issue
10
Pages
1289-1293
ISSN
0026-0495 (ISSN-L)
DOI
10.1016/s0026-0495(98)90338-9
OpenAlex
W2082459661
Semantic Scholar
8dfa261eadbc4019e1ab4161e0644c6c92be3ba4
Cited by
95
References
30
Citations by year
2026: 1 · 2025: 1 · 2024: 2 · 2022: 3 · 2021: 6 · 2020: 1 · 2019: 2 · 2018: 1 · 2017: 3 · 2016: 6 · 2015: 8 · 2014: 5 · 2013: 1 · 2012: 3
FWCI
2.46
Type
journal article
Language
en
Open access
closed
Licence
Locations
  • Metabolism (publishedVersion)
  • PubMed (publishedVersion)
Topics
  • Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Thyroid Disorders and Treatments
  • Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Adrenal Hormones and Disorders
  • Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Growth Hormone and Insulin-like Growth Factors
Keywords
interleukin-6, thyroid function, low T3 syndrome, thyroid-stimulating hormone, free thyroxine, triiodothyronine, reverse T3, thyroxine-binding globulin, hypothalamic-pituitary-adrenal axis, acute phase response, healthy volunteers, single injection, TSH suppression
MeSH terms
Adult, Body Temperature, Female, Hemodynamics, Humans, Hydrocortisone, Male, Thyroid Gland, Thyrotropin, Thyroxine-Binding Proteins, Interleukin-6

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