Premium
Increased thyroidal fat and goitrous hypothyroidism induced by interferon‐γ
Author(s) -
Kimura Hiroaki,
Kimura Miho,
Westra William H.,
Rose Noel R.,
Caturegli Patrizio
Publication year - 2005
Publication title -
international journal of experimental pathology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.671
H-Index - 72
eISSN - 1365-2613
pISSN - 0959-9673
DOI - 10.1111/j.0959-9673.2005.00418.x
Subject(s) - thyroid , thyroglobulin , medicine , endocrinology , infiltration (hvac) , autoimmune thyroiditis , stroma , transgene , thyroiditis , genetically modified mouse , inflammation , adipocyte , adipose tissue , immunohistochemistry , biology , biochemistry , physics , gene , thermodynamics
Summary Hashimoto's thyroiditis is associated with a diffuse lymphocytic infiltration of the stroma and a production of several cytokines, such as interferon‐γ (IFN‐γ). We previously reported that transgenic mice expressing IFN‐γ under the control of the thyroglobulin promoter develop primary hypothyroidism. In order to determine the long‐term changes induced by IFN‐γ in the thyroid gland, we analysed cross‐sectionally 202 mice (96 transgenic mice and 106 controls) of 0–650 days of age. Multiple linear regression analysis showed that, after adjusting for age and sex, thyr ‐IFN‐γ transgenic mice were 14% (3 g) smaller ( P < 0.0001) and had a 5‐ to 6‐fold bigger thyroid ( P < 0.0001) than wild‐type littermates. Transgenic thyroids showed striking histopathological changes in follicles, thyrocytes and stroma. Follicles were enlarged, irregular and were lined by thickened, granular and oxyphilic thyrocytes. The stroma contained a moderate and diffuse mononuclear infiltrate – mainly composed of macrophages – and, interestingly, a clear increase in the content of fat. These findings indicate that, in addition to hypothyroidism, chronic exposure of the thyroid to IFN‐γ leads also to macrophage infiltration and subsequent adipocyte expansion, suggesting a link between inflammation and fat accumulation.