Boelen A, Platvoet-ter Schiphorst M C, van Rooijen N, Wiersinga W M
Department of Endocrinology, Academic Medical Center, University of Amsterdam, The Netherlands.
Eur J Endocrinol. 1996 Apr;134(4):513-8. doi: 10.1530/eje.0.1340513.
A decreased serum triiodothyronine (T3) level is one of the main characteristics of the sick euthyroid syndrome, caused mainly by a decreased 5'-deiodination of thyroxine (T4) in the liver. Cytokines have been implicated in the pathogenesis of the changes in thyroid hormone metabolism during illness. We therefore investigated the role of cytokines produced by the liver macrophages (Kupffer cells) in the development of the sick euthyroid syndrome, which was induced in mice by a single injection of bacterial endotoxin (lipopolysaccharide) or by 24-h starvation. Experiments were carried out with or without previous selective depletion of liver macrophages by intravenous administration of liposome-encapsulated dichloromethylene diphosphonate. Relative to saline-injected pair-fed controls, the administration of lipopolysaccharide caused a decrease of serum T3 and T4 and liver 5'-deiodinase mRNA. Selective depletion of liver macrophages, did not affect these changes. Starvation for 24h decreased serum T3 and T4, associated with a slight decrease of liver 5'-deiodinase mRNA. There were no differences between macrophage-depleted and non-depleted animals in this respect. In summary, selective depletion of liver macrophages did not affect the decrease in serum T3, T4 or liver 5'-deiodinase mRNA induced by lipopolysaccharide or 24-h starvation in mice. We conclude that cytokines produced by Kupffer cells are not involved in the pathogenesis of the sick euthyroid syndrome in this experimental model.
血清三碘甲状腺原氨酸（T3）水平降低是低甲状腺素病态综合征的主要特征之一，主要由肝脏中甲状腺素（T4）的5'-脱碘作用降低所致。细胞因子与疾病期间甲状腺激素代谢变化的发病机制有关。因此，我们研究了肝脏巨噬细胞（库普弗细胞）产生的细胞因子在低甲状腺素病态综合征发生发展中的作用，该综合征是通过单次注射细菌内毒素（脂多糖）或24小时饥饿在小鼠中诱导产生的。实验在静脉注射脂质体包裹的二氯亚甲基二膦酸盐选择性清除肝脏巨噬细胞前后进行。相对于注射生理盐水的配对喂养对照组，脂多糖给药导致血清T3和T4以及肝脏5'-脱碘酶mRNA水平降低。肝脏巨噬细胞的选择性清除并未影响这些变化。饥饿24小时会降低血清T3和T4，同时肝脏5'-脱碘酶mRNA略有下降。在这方面，巨噬细胞清除组和未清除组动物之间没有差异。总之，肝脏巨噬细胞的选择性清除并未影响脂多糖或24小时饥饿诱导的小鼠血清T3、T4或肝脏5'-脱碘酶mRNA的降低。我们得出结论，在这个实验模型中，库普弗细胞产生的细胞因子不参与低甲状腺素病态综合征的发病机制。
