ArticleThe Journal of clinical investigation2011
IL-6 promotes nonthyroidal illness syndrome by blocking thyroxine activation while promoting thyroid hormone inactivation in human cells.
Article in The Journal of clinical investigation, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT01501110 (Evaluation of the Effects of N-acetylcysteine on Thyroid Hormone Levels in the Low T3 Syndrome), which is not on this map. Cited by 79 papers, 1 of them a synthesis that pooled it.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Evaluation of the Effects of N-acetylcysteine on Thyroid Hormone Levels in the Low T3 Syndrome
Who cites it
79 citing papers in PubMed, 1 synthesis or guideline pooled it, 159 citations in OpenAlex.
- Association of thyroid hormones and thyroid-stimulating hormone with mortality in adults admitted to the intensive care unit: A systematic review and meta-analysis.Journal of the Chinese Medical Association : JCMA · 2022Pooled it
- Treatment for non-thyroidal illness syndrome in advanced chronic kidney disease: a single-blind controlled study.Journal of nephrology · 2017Trial
- N-acetylcysteine administration prevents nonthyroidal illness syndrome in patients with acute myocardial infarction: a randomized clinical trial.The Journal of clinical endocrinology and metabolism · 2014Trial
- Association between annual air pollutant exposure and thyroid function: a retrospective cross-sectional study.Journal of endocrinological investigation · 2026Article
- Peripheral Hematological and Immune-Endocrine Markers in Children with Specific Learning Disorder: An Exploratory Retrospective Case-Control Study.Brain sciences · 2026Article
- Article
- Endocrine disruptions in thermal injuries: exploring immune system interactions.Physiological reviews · 2026Review
- Early total triiodothyronine, illness severity, and in-hospital mortality in critically ill adults.Scientific reports · 2026Article
- Left Atrial Deformation Parameters After Myocardial Infarction With Low Triiodothyronine Syndrome and Their Prognostic Value.Cardiology research · 2026Article
- Association between impaired peripheral thyroid hormone sensitivity and coronary heart disease in type 2 diabetes: the potential mediating role of albumin.Frontiers in endocrinology · 2026Article
- Long-term trajectories of reproductive and pituitary-adrenal-thyroid hormones in young males following Omicron BA.2 infection: a two-year prospective cohort study.Frontiers in endocrinology · 2026Article
- Risk Factors of Thyroid Dysfunction in Patients with Acute Pancreatitis and Predictive Value of TSH for Disease Severity.Risk management and healthcare policy · 2026Article
- An Unusual Presentation of Severe Hypothyroidism in a Child With Undiagnosed Systemic Lupus Erythematous.JCEM case reports · 2026Article
- Unilateral hilar sarcoidosis with anemia and low T3 syndrome: a case report.Frontiers in medicine · 2026Article
- Thyroid-Microbiome Allostasis and Mitochondrial Performance: An Integrative Perspective in Exercise Physiology.Nutrients · 2025Review
- Dissecting biomarker networks linking COVID-19 inflammatory drivers, disease severity and thyroid adaptive responses.Scientific reports · 2025Article
- Euthyroid Sick Syndrome as an Index of Prognosis in Severe COVID-19 Disease.Medicina (Kaunas, Lithuania) · 2025Article
- ICU 'Magic Numbers': The Role of Biomarkers in Supporting Clinical Decision-Making.Diagnostics (Basel, Switzerland) · 2025Review
- Induction of type 2 and 3 deiodinase in the blood cells of critically ill patients.Endocrine connections · 2025Article
- Body roundness index, thyroid hormones, and threshold effects in US adults: a cross-sectional study from NHANES.Frontiers in nutrition · 2025Article
19 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
5 authors at 3 institutions in 2 countries.
Funding
Abstract
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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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.