Increased thyroidal fat and goitrous hypothyroidism induced by interferon-gamma.
Summary Hashimoto's thyroiditis is associated with a diffuse lymphocytic infiltration of the stroma and a production of several cytokines, such as interferon-gamma (IFN-gamma). We previously reported that transgenic mice expressing IFN-gamma under the control of the thyroglobulin promoter develop primary hypothyroidism. In order to determine the long-term changes induced by IFN-gamma 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-gamma 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-gamma leads also to macrophage infiltration and subsequent adipocyte expansion, suggesting a link between inflammation and fat accumulation.
Kimura
Hiroaki
H
Department of Pathology, The Johns Hopkins Medical Institutions, Baltimore, MD, USA.
Kimura
Miho
M
Westra
William H
WH
Rose
Noel R
NR
Caturegli
Patrizio
P
D000273:Adipose Tissue / Q000473:pathology; D000818:Animals; D001323:Autoantibodies / Q000097:blood; D001835:Body Weight; D006130:Growth Disorders / Q000209:etiology / Q000276:immunology / Q000473:pathology; D007037:Hypothyroidism / Q000150:complications / Q000276:immunology* / Q000473:pathology; D007371:Interferon-gamma / Q000235:genetics / Q000276:immunology*; D008264:Macrophages / Q000276:immunology / Q000473:pathology; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D013961:Thyroid Gland / Q000276:immunology / Q000473:pathology*; D013967:Thyroiditis, Autoimmune / Q000150:complications / Q000276:immunology* / Q000473:pathology
D001323:Autoantibodies; D007371:Interferon-gamma