title: Induction of type 3 deiodinase activity in inflammatory cells of mice with chronic local inflammation.
abstract: 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 T(4) into T(3) 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-1beta and IL-6 mRNA expression. Inflammatory cells, surrounding the abscess showed D3 and T(3)-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 T(3).
authors.affiliation: Department of Endocrinology and Metabolism, Academic Medical Center, Amsterdam, The Netherlands. a.boelen@amc.uva.nl
authors.forename: A
authors.initials: A
authors.lastname: Boelen
authors.forename: J
authors.initials: J
authors.lastname: Kwakkel
authors.forename: A
authors.initials: A
authors.lastname: Alkemade
authors.forename: R
authors.initials: R
authors.lastname: Renckens
authors.forename: E
authors.initials: E
authors.lastname: Kaptein
authors.forename: G
authors.initials: G
authors.lastname: Kuiper
authors.forename: W M
authors.initials: WM
authors.lastname: Wiersinga
authors.forename: T J
authors.initials: TJ
authors.lastname: Visser
mesh_terms: D000038:Abscess / Q000139:chemically induced / Q000201:enzymology / Q000378:metabolism / Q000473:pathology; D000818:Animals; D002908:Chronic Disease; D005260:Female; D006614:Hindlimb; D007150:Immunohistochemistry; D007249:Inflammation / Q000139:chemically induced / Q000201:enzymology* / Q000473:pathology; D007274:Injections, Intraperitoneal; D007279:Injections, Subcutaneous; D007375:Interleukin-1 / Q000235:genetics; D015850:Interleukin-6 / Q000235:genetics; D007453:Iodide Peroxidase / Q000096:biosynthesis*; D007509:Irritants / Q000008:administration & dosage; D008070:Lipopolysaccharides / Q000008:administration & dosage; D008099:Liver / Q000201:enzymology; D026901:Membrane Transport Proteins / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D027501:Monocarboxylic Acid Transporters; D018482:Muscle, Skeletal / Q000201:enzymology; D009135:Muscular Diseases / Q000139:chemically induced / Q000201:enzymology / Q000378:metabolism / Q000473:pathology; D012333:RNA, Messenger / Q000378:metabolism; D040521:Subcutaneous Tissue / Q000201:enzymology; D027981:Symporters; D014425:Turpentine / Q000008:administration & dosage
chemical_list: D007375:Interleukin-1; D015850:Interleukin-6; D007509:Irritants; D008070:Lipopolysaccharides; D026901:Membrane Transport Proteins; D027501:Monocarboxylic Acid Transporters; D012333:RNA, Messenger; C484257:Slc16a2 protein, mouse; D027981:Symporters; C117274:iodothyronine deiodinase type III; D007453:Iodide Peroxidase; D014425:Turpentine