Contribution of Interleukin-12 to the Pathogenesis of Non-thyroidal Illness

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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