Selective macrophage depletion in the liver does not prevent the development of the sick euthyroid syndrome in the mouse

A decreased serum triiodothyronine (T-3) level is one of the main characteristics of the sick euthyroid syndrome, caused mainly by a decreased 5'-deiodination of thyroxine (T-4) in the liver, Cytokines have been implicated in the pathogenesis of the changes in thyroid hormone metabolism during illness. Mie 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 T-3 and T-4 and liver 5'-deiodinase mRNA. Selective depletion of liner macrophages did not affect these changes. Starvation for 24 h decreased serum T-3 and T-4, 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 T-3, T-4 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.