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• W2114397821 startingPage "1834" @default.
• W2114397821 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. Iodothyronine 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." @default.
• W2114397821 created "2016-06-24" @default.
• W2114397821 creator A5003076812 @default.
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• W2114397821 creator A5040787757 @default.
• W2114397821 creator A5061275843 @default.
• W2114397821 creator A5067415891 @default.
• W2114397821 date "2011-05-02" @default.
• W2114397821 modified "2023-10-17" @default.
• W2114397821 title "IL-6 promotes nonthyroidal illness syndrome by blocking thyroxine activation while promoting thyroid hormone inactivation in human cells" @default.
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• W2114397821 doi "https://doi.org/10.1172/jci44678" @default.
• W2114397821 hasPubMedCentralId "https://www.ncbi.nlm.nih.gov/pmc/articles/3083773" @default.
• W2114397821 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/21540553" @default.
• W2114397821 hasPublicationYear "2011" @default.
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