Abstract
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, TNFα and IFNγ. IL-12 is involved in
regulation of IFNγ and TNFα. 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 T3, T4 and liver 5′-DI mRNA expression in IL-12-/- and WT mice with the exception of a smaller reduction of serum T4 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 T4 decrease. In conclusion, IL-12 is involved in the central regulation of the HPT axis
during illness but not in the peripheral regulation.
Key words
5′-deiodinase - Pituitary - Liver - Cytokines - IL-12-/- mice
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Dr. A. Boelen
Department of Endocrinology & Metabolism · F5-171, Academic Medical Center ·
Meibergdreef 9 · 1105 AZ Amsterdam · The Netherlands
Phone: + 31 (20) 566 57 49 ·
Email: a.boelen@amc.uva.nl
