The Effects of Alpha Interferon on the Development of Autoimmune Thyroiditis in the NOD H2h4 Mouse

Alpha interferon (αIFN) therapy is known to induce thyroid autoimmunity in up to 40% of patients. The mechanism is unknown, but Th1 switching has been hypothesized. The aim of our study was to examine whether αIFN accelerated the development of thyroiditis in genetically susceptible mice. We took ad...

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Main Authors: Yael Oppenheim, Grace Kim, Yoshiyuki Ban, Pamela Unger, Erlinda Concepcion, Takao Ando, Yaron Tomer
Format: Article
Language:English
Published: Wiley 2003-01-01
Series:Clinical and Developmental Immunology
Online Access:http://dx.doi.org/10.1080/10446670310001642177
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author Yael Oppenheim
Grace Kim
Yoshiyuki Ban
Pamela Unger
Erlinda Concepcion
Takao Ando
Yaron Tomer
author_facet Yael Oppenheim
Grace Kim
Yoshiyuki Ban
Pamela Unger
Erlinda Concepcion
Takao Ando
Yaron Tomer
author_sort Yael Oppenheim
collection DOAJ
description Alpha interferon (αIFN) therapy is known to induce thyroid autoimmunity in up to 40% of patients. The mechanism is unknown, but Th1 switching has been hypothesized. The aim of our study was to examine whether αIFN accelerated the development of thyroiditis in genetically susceptible mice. We took advantage of NOD-H2h4, a genetically susceptible animal model, which develops thyroiditis when fed a high iodine diet. Six to eight week old male NOD H2h4 mice were injected with mouse αIFN (200 units) or with saline three times a week for 8 weeks. All mice drank iodinated water (0.15%). Mice were sacrificed after 8 weeks of injection. Their thyroids were examined for histology and blood was tested for antithyroglobulin antibody levels. T4 and glucose levels were also assessed. In the IFN-injected group, 6/13 (46.2%) developed thyroiditis and/or thyroid antibodies while in the saline-injected group, only 4/13 (30.8%) developed thyroiditis and/or thyroid antibodies (p=0.4). The grade of thyroiditis was not different amongst the two groups. None of the mice developed clinical thyroiditis or diabetes mellitus. Our results showed that αIFN treatment did not accelerate thyroiditis in this mouse model. This may imply that αIFN induces thyroiditis in a non-genetically dependent manner, and this would not be detected in a genetically susceptible mouse model if the effect were small. Alternatively, it is possible that αIFN did not induce thyroiditis in mice because, unlike in humans, in mice αIFN does not induce Th1 switching.
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spelling doaj-art-271ab987b786479ebfd4ab17fbaaeec92025-02-03T01:27:10ZengWileyClinical and Developmental Immunology1740-25221740-25302003-01-01102-416116510.1080/10446670310001642177The Effects of Alpha Interferon on the Development of Autoimmune Thyroiditis in the NOD H2h4 MouseYael Oppenheim0Grace Kim1Yoshiyuki Ban2Pamela Unger3Erlinda Concepcion4Takao Ando5Yaron Tomer6Division of Endocrinology, Diabetes and Bone Diseases, New York, NY, USADivision of Endocrinology, Diabetes and Bone Diseases, New York, NY, USADivision of Endocrinology, Diabetes and Bone Diseases, New York, NY, USADepartment of Pathology, Mount Sinai School of Medicine, New York, NY, USADivision of Endocrinology, Diabetes and Bone Diseases, New York, NY, USADivision of Endocrinology, Diabetes and Bone Diseases, New York, NY, USADivision of Endocrinology, Diabetes and Bone Diseases, New York, NY, USAAlpha interferon (αIFN) therapy is known to induce thyroid autoimmunity in up to 40% of patients. The mechanism is unknown, but Th1 switching has been hypothesized. The aim of our study was to examine whether αIFN accelerated the development of thyroiditis in genetically susceptible mice. We took advantage of NOD-H2h4, a genetically susceptible animal model, which develops thyroiditis when fed a high iodine diet. Six to eight week old male NOD H2h4 mice were injected with mouse αIFN (200 units) or with saline three times a week for 8 weeks. All mice drank iodinated water (0.15%). Mice were sacrificed after 8 weeks of injection. Their thyroids were examined for histology and blood was tested for antithyroglobulin antibody levels. T4 and glucose levels were also assessed. In the IFN-injected group, 6/13 (46.2%) developed thyroiditis and/or thyroid antibodies while in the saline-injected group, only 4/13 (30.8%) developed thyroiditis and/or thyroid antibodies (p=0.4). The grade of thyroiditis was not different amongst the two groups. None of the mice developed clinical thyroiditis or diabetes mellitus. Our results showed that αIFN treatment did not accelerate thyroiditis in this mouse model. This may imply that αIFN induces thyroiditis in a non-genetically dependent manner, and this would not be detected in a genetically susceptible mouse model if the effect were small. Alternatively, it is possible that αIFN did not induce thyroiditis in mice because, unlike in humans, in mice αIFN does not induce Th1 switching.http://dx.doi.org/10.1080/10446670310001642177
spellingShingle Yael Oppenheim
Grace Kim
Yoshiyuki Ban
Pamela Unger
Erlinda Concepcion
Takao Ando
Yaron Tomer
The Effects of Alpha Interferon on the Development of Autoimmune Thyroiditis in the NOD H2h4 Mouse
Clinical and Developmental Immunology
title The Effects of Alpha Interferon on the Development of Autoimmune Thyroiditis in the NOD H2h4 Mouse
title_full The Effects of Alpha Interferon on the Development of Autoimmune Thyroiditis in the NOD H2h4 Mouse
title_fullStr The Effects of Alpha Interferon on the Development of Autoimmune Thyroiditis in the NOD H2h4 Mouse
title_full_unstemmed The Effects of Alpha Interferon on the Development of Autoimmune Thyroiditis in the NOD H2h4 Mouse
title_short The Effects of Alpha Interferon on the Development of Autoimmune Thyroiditis in the NOD H2h4 Mouse
title_sort effects of alpha interferon on the development of autoimmune thyroiditis in the nod h2h4 mouse
url http://dx.doi.org/10.1080/10446670310001642177
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