Different effects of continuous infusion of interleukin-1 and interleukin-6 on the hypothalamic-hypophysial-thyroid axis.
Open accessAbstract
The cytokines interleukin-1 (IL-1) and IL-6 are thought to be important mediators in the suppression of thyroid function during nonthyroidal illness. In this study we compared the effects of IL-1 and IL-6 infusion on the hypothalamus-pituitary-thyroid axis in rats. Cytokines were administered by continuous ip infusion of 4 micrograms IL-1 alpha/day for 1, 2, or 7 days or of 15 micrograms IL-6/day for 7 days. Body weight and temperature, food and water intake, and plasma TSH, T4, free T4 (FT4), T3, and corticosterone levels were measured daily, and hypothalamic pro-TRH messenger RNA (mRNA) and hypophysial TSH beta mRNA were determined after termination of the experiments. Compared with saline-treated controls, infusion of IL-1, but not of IL-6, produced a transient decrease in food and water intake, a transient increase in body temperature, and a prolonged decrease in body weight. Both cytokines caused transient decreases in plasma TSH and T4, which were greater and more prolonged with IL-1 than with IL-6, whereas they effected similar transient increases in the plasma FT4 fraction. Infusion with IL-1, but not IL-6, also induced transient decreases in plasma FT4 and T3 and a transient increase in plasma corticosterone. Hypothalamic pro-TRH mRNA was significantly decreased (-73%) after 7 days, but not after 1 or 2 days, of IL-1 infusion and was unaffected by IL-6 infusion. Hypophysial TSH beta mRNA was significantly decreased after 2 (-62%) and 7 (-62%) days, but not after 1 day, of IL-1 infusion and was unaffected by IL-6 infusion. These results are in agreement with previous findings that IL-1, more so than IL-6, directly inhibits thyroid hormone production. They also indicate that IL-1 and IL-6 both decrease plasma T4 binding. Furthermore, both cytokines induce an acute and dramatic decrease in plasma TSH before (IL-1) or even without (IL-6) a decrease in hypothalamic pro-TRH mRNA or hypophysial TSH beta mRNA, suggesting that the acute decrease in TSH secretion is not caused by decreased pro-TRH and TSH beta gene expression. The TSH-suppressive effect of IL-6, either administered as such or induced by IL-1 infusion, may be due to a direct effect on the thyrotroph, whereas additional effects of IL-1 may involve changes in the hypothalamic release of somatostatin or TRH.(ABSTRACT TRUNCATED AT 400 WORDS)
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Chronic IL-6 infusions result in decreased serum T4, T3 and hypothalamic TRH expression in rats.
“In support of an important role for IL-6, chronic IL-6 infusions result in decreased serum T4, T3 and hypothalamic TRH expression in rats [53].”
From An update on non-thyroidal illness syndrome (2021) · cites this paper as [53]
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- Authors
- van Haasteren, G. A., van der Meer, M. J., Hermus, A. R., Linkels, E., Klootwijk, W., Kaptein, E., van Toor, H., Sweep, C. G., Visser, T. J., & de Greef, W. J.
- Affiliations
- Erasmus University Rotterdam (NL)
- ORCID
- Hermus, A R
- Venue
- Endocrinology
- Publisher
- The Endocrine Society
- Published
- 1994-10
- Volume
- 135
- Issue
- 4
- Pages
- 1336-1345
- ISSN
- 0013-7227 (ISSN-L)
- 1945-7170
- OpenAlex
- W2095656220
- Cited by
- 69
- References
- 33
- Citations by year
- 2026: 1 · 2024: 1 · 2022: 3 · 2020: 2 · 2019: 1 · 2018: 2 · 2017: 3 · 2016: 2 · 2015: 2 · 2013: 2 · 2012: 2
- FWCI
- 2.93
- Type
- journal article
- Language
- en
- Open access
- green
- hdl.handle.net
- Licence
- other-oa
- Locations
- Endocrinology (publishedVersion)
- PubMed (publishedVersion)
- RePub (Erasmus University Rotterdam) (submittedVersion, other-oa)
- RePub (Erasmus University Rotterdam) (submittedVersion)
- Topics
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Thyroid Disorders and Treatments
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Growth Hormone and Insulin-like Growth Factors
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Adrenal Hormones and Disorders
- Keywords
- interleukin-1, interleukin-6, hypothalamic-pituitary-thyroid axis, low T3 syndrome, thyroid suppression, TSH secretion, thyroid hormone binding, free thyroxine, corticosterone, food and water intake, body temperature, body weight, rats
- MeSH terms
- Animals, Body Temperature, Body Weight, Corticosterone, Drinking, Eating, Hypothalamo-Hypophyseal System, Hypothalamus, Interleukin-1, Male, Median Eminence, Pituitary Gland, Protein Precursors, Pyrrolidonecarboxylic Acid, Radioimmunoassay, RNA, Messenger, Thyroid Gland, Thyrotropin, Thyrotropin-Releasing Hormone, Thyroxine, Triiodothyronine, Interleukin-6, Gene Expression, Rats, Wistar, Rats
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