Contribution of interleukin-12 to the pathogenesis of non-thyroidal illness.
Changes in both central and peripheral thyroid hormone (TH) metabolism occur during illness. These changes, known collectively as non-thyroidal illness, are apparently mediated by the proinflammatory cytokines IL-6, TNFalpha and IFNgamma. IL-12 is involved in regulation of IFNgamma and TNFalpha. The aim of this study was to evaluate the role of IL-12 in TH metabolism during illness. We studied TH metabolism both centrally (in the pituitary) and peripherally (in the liver) in IL-12 knock-out (IL-12 (-/-)) and wild type (WT) mice during illness induced by administration of bacterial endotoxin (LPS). LPS induced a similar decrease in serum T (3), T (4) and liver 5'-DI mRNA expression in IL-12 (-/-) and WT mice with the exception of a smaller reduction of serum T (4) in IL-12 (-/-) mice. In the pituitary, the LPS-induced decline in 5'-DI activity in WT mice was not observed in IL-12 (-/-) mice (p < 0.001), whereas the decrease in DII activity tended to be smaller in IL-12 (-/-) mice (p = 0.066). The lower decrease in pituitary activity of both DI and DII in IL-12 (-/-) mice is possibly related to the lower LPS-induced T (4) decrease. In conclusion, IL-12 is involved in the central regulation of the HPT axis during illness but not in the peripheral regulation.
Department of Endocrinology & Metabolism, F5-171 Academic Medical Center, University of Amsterdam, Meibergdreef 9, 1105 AZ Amsterdam, The Netherlands. a.boelen@amc.uva.nl
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Boelen
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Kwakkel
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Platvoet-ter Schiphorst
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Baur
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Köhrle
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Wiersinga
D000818:Animals; D016207:Cytokines / Q000235:genetics; D005260:Female; D018664:Interleukin-12 / Q000378:metabolism*; D007453:Iodide Peroxidase / Q000378:metabolism; D007527:Isoenzymes / Q000378:metabolism; D008070:Lipopolysaccharides / Q000494:pharmacology*; D008099:Liver / Q000201:enzymology; D051379:Mice; D008807:Mice, Inbred BALB C; D018345:Mice, Knockout; D012333:RNA, Messenger / Q000037:antagonists & inhibitors; D013217:Starvation / Q000097:blood / Q000378:metabolism*; D013963:Thyroid Hormones / Q000097:blood*; D013974:Thyroxine / Q000037:antagonists & inhibitors / Q000097:blood; D014284:Triiodothyronine / Q000037:antagonists & inhibitors / Q000097:blood
D016207:Cytokines; D007527:Isoenzymes; D008070:Lipopolysaccharides; D012333:RNA, Messenger; D013963:Thyroid Hormones; D014284:Triiodothyronine; D018664:Interleukin-12; D007453:Iodide Peroxidase; D013974:Thyroxine