Induced illness in interleukin-6 (IL-6) knock-out mice: A causal role of IL-6 in the development of the low 3,5,3'-triiodothyronine syndrome
Induced illness in interleukin-6 (IL-6) knock-out mice: A causal role of IL-6 in the development of the low 3,5,3'-triiodothyronine syndrome
复制标题
DOI：
10.1210/en.137.12.5250
复制
发表时间：
1996-12-01
期刊：
影响因子：
4.8
通讯作者：
Wiersinga, WM
中科院分区：
文献类型：
--
作者：
Boelen, A;Maas, MAW;Wiersinga, WM
对人类受试者或实验动物给予白细胞介素-6（IL-6）可诱导甲状腺激素代谢发生类似于患病甲状腺功能正常综合征的变化。此外，疾病期间血清T-3的降低与血清IL-6浓度显著相关。这些发现表明，但不能证明，IL-6在发展中的因果关系。低T-3综合征本研究的目的是评估IL-6在IL-6基因敲除的病态甲状腺功能正常综合征发生中的作用。（IL-6（-/-））小鼠与野生型小鼠相比在IL-6（-/-）和IL-G（-/+）小鼠中通过1）施用细菌内毒素（LPS），2）感染单核细胞增生李斯特菌，（3）双后肢注射睾酮。在所有三个实验中，两组的食物摄入量保持相似。分别于24 h（LPS）、96 h（L.单核细胞增多症）和48小时（turfenic）。IL-6（+/+）小鼠血清IL-6对所有刺激均有反应性升高，但IL-6（-/-）小鼠血清IL-6水平无明显变化。两组血清肿瘤坏死因子-α的诱导程度相似，但L. nonocytogenes或turmonium给药。血清T-3和T-4在所有三种刺激后均下降。IL-6（-/-）小鼠血清T-4的降低与IL-6（+/+）小鼠相似。然而，IL-6（-/-）小鼠血清T-3的降低小于IL-6（+/+）小鼠; LPS处理后24小时，T-3水平分别为1.56 ± 0.29和0.99 ± 0.15 nmol/L（P < 0.01），96 h后分别为2.39 ± 0.17和1.75 ± 0.24nmol/L。单核细胞增多症治疗后48 h分别为1.46 ± 0.18和1.10 ± 0.25nmol/L（P < 0.05）。IL-6（-/-）小鼠中血清T-3的较小下降不能归因于诱导疾病的严重程度、食物摄入或皮质酮反应的差异，这些在IL-6（-/-）小鼠和IL-6（-/+）小鼠中均相似。肝5 '-脱碘酶mRNA在所有三种刺激后均下降; IL-6（-/-）小鼠中单核细胞增多症感染较小，但IL-6（+/+）小鼠中的差异未达到统计学显著性。在野生型动物中，注射姜黄素后肝脏5 ′-脱碘酶活性降低了36%，但在敲除小鼠中没有变化。总之，急性诱导的疾病产生低T-3综合征，这在IL-6敲除小鼠中比野生型小鼠中更不明显。这些数据表明IL-6在低T-3综合征的发展中起因果作用。
Interleukin-6 (IL-6) administration to human subjects or experimental animals induces changes in thyroid hormone metabolism resembling those in the sick euthyroid syndrome. Furthermore, the decrease in serum T-3 during illness is significantly related to serum IL-6 concentrations. These findings suggest, but do not prove, a causal role for IL-6 in the development of. the low T-3 syndrome. The aim of the present study was to evaluate the role of IL-6 in the development of the sick euthyroid syndrome in IL-6 knock-out (IL-6(-/-)) mice compared to that in wild-type mice (IL-G(+/+)).Illness was induced in IL-6(-/-) and IL-G(-/+) mice by 1) administration of bacterial endotoxin (LPS), 2) infection with Listeria monocytogenes, and 3) turpentine injection in both hind limbs. Food intake was kept similar in both groups in all three experiments. Serial measurements were made of serum IL-6, tumor necrosis factor-alpha, T-3, T-4, corticosterone, and liver 5'-deiodinase (5'-DI) messenger RNA (mRNA) for 24 h (LPS), 96 h (L. monocytogenes), and 48 h (turpentine). Serum IL-6 increased in response to all stimuli in IL-6(+/+) mice, but not in IL-6(-/-) mice. Serum tumor necrosis factor-alpha was induced by LPS in both groups to a similar extent, but did not rise after L. nonocytogenes or turpentine administration. Serum T-3 and T-4 decreased after all three stimuli. The decrease in serum T-4 in IL-6(-/-) was similar to that in IL-6(+/+) mice. The decrease in serum T-3, however, was smaller in the IL-6(-/-) mice than in the IL-6(+/+) mice; T-3 levels were 1.56 +/- 0.29 and 0.99 +/- 0.15 nmol/liter, respectively, 24 h after LPS treatment (P < 0.01), 2.39 +/- 0.17 and 1.75 +/- 0.24 nmol/liter 96 h after L. monocytogenes treatment (P < 0.01), and 1.46 +/- 0.18 and 1.10 +/- 0.25 nmol/liter 48 h after turpentine treatment (P < 0.05). The smaller fall in serum T-3 in IL-6(-/-) mice could not be attributed to differences in the severity of the induced illness, food intake, or corticosterone response, which were all similar in IL-6(-/-) mice and IL-6(-/+) mice. Liver 5'-deiodinase mRNA decreased after all three stimuli; the decrease after LPS and L. monocytogenes infection was smaller in the IL-6(-/-) mice, but the difference in IL-6(+/+) mice just failed to reached statistical significance. Liver 5'-deiodinase activity after turpentine injection administration decreased in the wild-type animals by 36%, but did not change in the knock-out mice.In conclusion, acutely induced illness generates the low T-3 Syndrome, which is less marked in IL-6 knock-out mice than in wild-type mice. The data suggest a causal role of IL-6 in the development of the low T-3 syndrome.