Endocrine Abstracts

Introduction: Interleukine-4 (IL-4) a T-helper type 2 cytokine (Th2), has been implicated in the pathogenesis of autoimmune thyroid diseases (AITD). However, the role of IL-4 in Hashimoto’s thyroiditis (HT) pathogenesis remains controversial. In this study, we investigated whether a constitutive IL-4 overexpression in the thyroid tissue (Thyr-IL4) could influence the development of thyroiditis in resistant (C57BL/6) or susceptible (NOD.H2^h4) mouse strains.

Methods: Thyr-IL4 C57BL/6 parental strain and NOD.H2^h4 mice were exposed to 0.05% of NaI supplemented water during 8 and 16 weeks. Disease development was evaluated by measuring serum TgAbs, as well as quantifying the immune cell infiltration by immunostaining, flow cytometry and cytokine mRNA expression. Thyroid function was also evaluated through serum TSH levels as well as mRNA expression of thyroid differentiation markers.

Results: After 16 weeks of NaI treatment circulating TgAbs were significantly higher in transgenic susceptible NOD.H2^h4 animals. NOD.H2^h4 Thyr-IL4 mice developed also intense lymphocytic infiltration. Moreover the relative mRNA expression of IFNγ, IL-10, TGFβ, TNFα, IL-17 and IL-13 was also significantly increased in treated transgenic animals compared to WT mice. Chronic administration of iodide induced an important increase in serum TSH levels in transgenic NOD.^H2h4 animals with the development of large colloid goiter. In addition, as expected in the escape from the Wolff-Chaikoff block, mRNA expression of the iodide symporter Nis was reduced in both WT and Thyr-IL4 animals. In contrast, for the thyroiditis resistant parental strain, no circulating TgAbs could be detected in the serum of WT and transgenic C57BL/6 mice. As previously reported, WT C57BL/6 animals did not show thyroidal leukocyte infiltrates 16 weeks after NaI treatment. Surprisingly, the transgenic parental strain shown intense leukocyte infiltration scattered throughout the thyroid tissue associated with enhanced expression of IFNγ, TGFβ, TNFα, IL-5 and IL-13. Thyr-IL4 C57BL/6 animals developed also thyroid goiter with increased TSH levels. However, instead of a correct Wolff-Chaikoff escape present in WT animals, the Nis mRNA expression remained elevated in transgenic mice.

Conclusions: We have shown that prolonged expression of IL-4 in the thyroid associated to a chronic administration of iodide exacerbate thyroiditis disease in spontaneous NOD.H2^h4 mice and can induced non-autoimmune thyroid infiltrate in C57BL/6 resistant genetic background.