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 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.