During illness, changes in thyroid hormone metabolism occur, so-called nonthyroidal illness (NTI). NTI has been characterized by a fall of serum T 3 due to decreased extrathyroidal conversion of T4 into T3 by liver type 1 deiodinase (D1), without an increase in serum TSH. Type 3 deiodinase (D3) was thought not to play an important role during NTI, but recently it has been shown that D3 activity is up-regulated in liver and skeletal muscle of critically ill patients related to hypoxia. We studied D3 gene expression and activity in liver and muscle/subcutis of mice during illness, which was induced by two different stimuli: bacterial endotoxin (lipopolysaccharide) administration, resulting in an acute systemic response, and a turpentine injection in each hindlimb, resulting in a local sc abscess. Lipopolysaccharide induced a rapid decrease in liver D1 and D3 activity but not skeletal muscle of hindlimb. In contrast, local inflammation induced by turpentine did not decrease liver D1 and D3 activity but increased markedly D3 activity in the muscle/subcutis sample containing the abscess, associated with strongly increased IL-1β and IL-6 mRNA expression. Inflammatory cells, surrounding the abscess showed D3 and T3-transporter monocarboxylate transporter-8 immunoreactivity, whereas muscle cells did not show any immunoreactivity. In conclusion, local inflammation strongly induces D3 activity in inflammatory cells, especially in invading polymorphonuclear granulocytes, suggesting enhanced local degradation of T3. Copyright

dx.doi.org/10.1210/en.2005-0608, hdl.handle.net/1765/65270
Endocrinology
Department of Internal Medicine

Boelen, A, Kwakkel, J, Alkemade, A, Renckens, R, Kaptein, E, Kuiper, G.G.J.M, … Visser, T.J. (2005). Induction of type 3 deiodinase activity in inflammatory cells of mice with chronic local inflammation. Endocrinology, 146(12), 5128–5134. doi:10.1210/en.2005-0608