The DOI matches its Crossref record; 73 of the 74 references it cites were found in a registry or an index.
IL-6 promotes nonthyroidal illness syndrome by blocking thyroxine activation while promoting thyroid hormone inactivation in human cells
Open accessAbstract
Nonthyroidal illness syndrome (NTIS) is a state of low serum 3,5,3' triiodothyronine (T₃) that occurs in chronically ill patients; the degree of reduction in T₃ is associated with overall prognosis and survival. Iodthyronine deiodinases are enzymes that catalyze iodine removal from thyroid hormones; type I and II deiodinase (D1 and D2, respectively) convert the prohormone thyroxine T₄ to active T₃, whereas the type III enzyme (D3) inactivates T₄ and T₃. Increased production of cytokines, including IL-6, is a hallmark of the acute phase of NTIS, but the role of cytokines in altered thyroid hormone metabolism is poorly understood. Here, we measured the effect of IL-6 on both endogenous cofactor-mediated and dithiothreitol-stimulated (DTT-stimulated) cell sonicate deiodinase activities in human cell lines. Active T₃ generation by D1 and D2 in intact cells was suppressed by IL-6, despite an increase in sonicate deiodinases (and mRNAs). N-acetyl-cysteine (NAC), an antioxidant that restores intracellular glutathione (GSH) concentrations, prevented the IL-6-induced inhibitory effect on D1- and D2-mediated T₃ production, which suggests that IL-6 might function by depleting an intracellular thiol cofactor, perhaps GSH. In contrast, IL-6 stimulated endogenous D3-mediated inactivation of T₃. Taken together, these results identify a single pathway by which IL-6-induced oxidative stress can reduce D1- and D2-mediated T₄-to-T₃ conversion as well as increasing D3-mediated T₃ (and T₄) inactivation, thus mimicking events during illness.
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“In addition, decreased availability of glutathione (GSH), a co-factor required for DIO1 catalytic activity, may also play a role [80].”
From An update on non-thyroidal illness syndrome (2021) · cites this paper as [80]
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Cites
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- 10.1210/me.14.11.1697 · DOI · Paper page
- 10.1210/en.133.4.1715 · DOI
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Cited by
Sorted by citations
Thyroid Hormones, Oxidative Stress, and Inflammation
Mancini, A., Segni, C. D., Raimondo, S., Olivieri, G., Silvestrini, A., Meucci, E., & Currò, D. (2016) · Mediators of Inflammation · doi:10.1155/2016/6757154 · Cited by 558
“This hypothesis is supported by the evidence that NAC, an antioxidant that restores intracellular GSH levels, prevents the IL-6-induced effects on the intracellular redox state [121, 122].”
BackgroundNon-Thyroidal Illness in the ICU: A Syndrome with Different Faces
Van den Berghe, G. (2014) · Thyroid® · doi:10.1089/thy.2014.0201 · Cited by 316
“Possible mediators of the acute fall in plasma T3 concentrations in critically ill patients include the release of cytokines, metabolites, and hypoxia-induced alterations (4,27,28).”
BackgroundBeyond Low Plasma T3: Local Thyroid Hormone Metabolism during Inflammation and Infection
Boelen, A., Kwakkel, J., & Fliers, E. (2011) · Endocrine Reviews · doi:10.1210/er.2011-0007 · Cited by 287
“First Published Online July 26, 2011 Abbreviations: AP-1, Activator protein-1; D1, deiodinase type 1; D2, deiodinase type 2; D3, deiodinase type 3; D3KO, D3 knockout; GHRP, GH-releasing peptide; GSH, glutathione; HIF, hypoxia inducible factor; HPT, hypothalamus pituitary thyroid; ICU, intensive care unit; IFN, infundi…”
BackgroundInfluentialRole of thyroid hormone in skeletal muscle physiology
Bloise, F. F., Cordeiro, A., & Ortiga-Carvalho, T. M. (2017) · Journal of Endocrinology · doi:10.1530/joe-16-0611 · Cited by 242
The teleost head kidney: Integrating thyroid and immune signalling
Geven, E. J. W., & Klaren, P. H. M. (2016) · Developmental & Comparative Immunology · doi:10.1016/j.dci.2016.06.025 · Cited by 214
“In mammalian thyrocytes, IL-6 exerts roughly the same repertoire of inhibitory effects as TNFa and IL-1b: inhibition of TPO gene expression (Tominaga et al., 1991), and inhibition of basal and TSHinduced 50-deiodination (Hashimoto et al., 1995; Wajner et al., 2011).”
Background
Metadata
- Authors
- Wajner, S. M., Goemann, I. M., Bueno, A. L., Larsen, P. R., & Maia, A. L.
- Affiliations
- Universidade Federal do Rio Grande do Sul (BR)
- Brigham and Women's Hospital (US)
- Corresponding author
- Maia, Ana Luiza
- Venue
- Journal of Clinical Investigation
- Published
- 2011-05-02
- Volume
- 121
- Issue
- 5
- Pages
- 1834-1845
- ISSN
- 0021-9738 (ISSN-L)
- PMC
- PMC3083773
- OpenAlex
- W2114397821
- Cited by
- 168
- References
- 74
- Citations by year
- 2026: 14 · 2025: 11 · 2024: 13 · 2023: 13 · 2022: 13 · 2021: 10 · 2020: 11 · 2019: 6 · 2018: 15 · 2017: 13 · 2016: 18 · 2015: 9 · 2014: 6 · 2013: 6 · 2012: 8
- FWCI
- 5.77
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Journal of Clinical Investigation (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Dartmouth College
- Coordenação de Aperfeiçoamento de Pessoal de Nível Superior
- Conselho Nacional de Desenvolvimento Científico e Tecnológico
- Fundação de Amparo à Pesquisa do Estado do Rio Grande do Sul
- Universidade Federal do Rio Grande do Sul
- Fundação Instituto de Pesquisas Econômicas
- National Institutes of Health
- Fogarty International Center (R03TW007559, TW007559)
- National Institute of Diabetes and Digestive and Kidney Diseases (DK36256, R01DK036256)
- 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
- low T3 syndrome, interleukin-6, thyroid hormone metabolism, deiodinases, type I deiodinase, type 2 deiodinase, type III deiodinase, triiodothyronine, thyroxine, oxidative stress, glutathione, N-acetylcysteine, cytokines, thyroid hormone inactivation
- MeSH terms
- Acetylcysteine, Cell Line, Dithiothreitol, Glutathione, Humans, RNA, Messenger, Thyroid Diseases, Thyroid Hormones, Thyroxine, Interleukin-6, Cytokines, Reactive Oxygen Species, Oxidative Stress, Cell Line, Tumor
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