The effects of alpha interferon on the development of autoimmune thyroiditis in the NOD H2h4 mouse.
Alpha interferon (alphaIFN) 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 alphaIFN 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 alphaIFN (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 alphaIFN treatment did not accelerate thyroiditis in this mouse model. This may imply that alphaIFN 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 alphaIFN did not induce thyroiditis in mice because, unlike in humans, in mice alphaIFN does not induce Th1 switching.
Oppenheim
Yael
Y
Division of Endocrinology, Diabetes, and Bone Diseases, New York, NY, USA.
Kim
Grace
G
Ban
Yoshiyuki
Y
Unger
Pamela
P
Concepcion
Erlinda
E
Ando
Takao
T
Tomer
Yaron
Y
D000818:Animals; D001323:Autoantibodies / Q000097:blood / Q000276:immunology; D001786:Blood Glucose / Q000378:metabolism; D015704:CD4 Antigens / Q000378:metabolism; D016898:Interferon-alpha / Q000009:adverse effects* / Q000276:immunology / Q000494:pharmacology*; D007455:Iodine / Q000627:therapeutic use; D008297:Male; D051379:Mice; D016688:Mice, Inbred NOD; D013967:Thyroiditis, Autoimmune / Q000139:chemically induced* / Q000188:drug therapy / Q000276:immunology* / Q000473:pathology
D001323:Autoantibodies; D001786:Blood Glucose; D015704:CD4 Antigens; D016898:Interferon-alpha; D007455:Iodine