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首页> 外文期刊>The journal of clinical investigation >IL-6 promotes nonthyroidal illness syndrome by blocking thyroxine activation while promoting thyroid hormone inactivation in human cells
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IL-6 promotes nonthyroidal illness syndrome by blocking thyroxine activation while promoting thyroid hormone inactivation in human cells

机译：IL-6通过阻断甲状腺素激活同时促进人体细胞甲状腺激素失活来促进非甲状腺疾病综合征

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Nonthyroidal illness syndrome (NTIS) is a state of low serum 3,5,3′ triiodothyronine (T_(3)) that occurs in chronically ill patients; the degree of reduction in T_(3) 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 T_(4) to active T_(3), whereas the type III enzyme (D3) inactivates T_(4) and T_(3). 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 T_(3) 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 T_(3) 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 T_(3). Taken together, these results identify a single pathway by which IL-6–induced oxidative stress can reduce D1- and D2-mediated T_(4)-to-T_(3) conversion as well as increasing D3-mediated T_(3) (and T_(4)) inactivation, thus mimicking events during illness.
机译：非甲状腺疾病综合征（NTIS）是一种在慢性病患者中出现的低血清3,5,3'三碘甲状腺素（T_（3））状态; T_（3）降低的程度与总体预后和生存率相关。碘甲状腺素脱碘酶是催化从甲状腺激素中去除碘的酶。 I型和II型脱碘酶（分别为D1和D2）将激素原甲状腺素T_（4）转化为活性T_（3），而III型酶（D3）使T_（4）和T_（3）失活。 NTIS急性期的特征是细胞因子（包括IL-6）的产量增加，但是人们对细胞因子在甲状腺激素代谢改变中的作用了解甚少。在这里，我们测量了IL-6对人细胞系中内源性辅因子介导的和二硫苏糖醇刺激的（DTT刺激的）细胞超声脱碘酶活性的影响。尽管超声去碘素酶（和mRNA）增加，但IL-6抑制了完整细胞中D1和D2产生的主动T_（3）。 N-乙酰半胱氨酸（NAC）是一种恢复细胞内谷胱甘肽（GSH）浓度的抗氧化剂，可阻止IL-6诱导的对D1和D2介导的T_（3）产生的抑制作用，这表明IL-6可能起作用通过消耗细胞内的巯基辅因子，也许是谷胱甘肽。相反，IL-6刺激内源性D3介导的T_（3）失活。综上所述，这些结果确定了IL-6诱导的氧化应激可以减少D1和D2介导的T_（4）到T_（3）转化以及增加D3介导的T_（3）的单一途径（和T_（4））失活，从而模仿疾病期间的事件。

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