Exacerbation of autoimmune thyroiditis by a single low dose of whole-body irradiation in non-obese diabetic-H2h4 mice

Int J Radiat Biol. 2008 Sep;84(9):761-9. doi: 10.1080/09553000802345910.

Abstract

Purpose: To evaluate how irradiation affects thyroid autoimmunity in mouse models of Hashimoto's thyroiditis and Graves' hyperthyroidism.

Materials and methods: Non-obese diabetic (NOD)-H2(h4) mice spontaneously develop anti-thyroglobulin (Tg) antibodies and thyroiditis when supplied with sodium iodine (NaI) in the drinking water. BALB/c mice develop anti-thyrotropin receptor (TSHR) antibodies and hyperthyroidism following immunization with adenovirus expressing TSHR (Ad-TSHR). Mice were irradiated as follows: A single whole-body irradiation with 0.05, 0.5 or 3 Gy one week before or after the beginning of NaI or immunization with Ad-TSHR, fractionated whole-body irradiations with 0.05 Gy twice a week or 0.5 Gy once a week from one week before NaI or Ad-TSHR immunization, or a single regional irradiation to the thyroid gland with 0.5 Gy one week before NaI. The effect of a single irradiation with 0.05, 0.5 or 3 Gy on splenocytes was also evaluated.

Results: A single whole-body irradiation with 0.5 Gy one week before NaI exacerbated thyroiditis and increased anti-Tg antibody titers in NOD-H2(h4) mice. In contrast, any irradiation protocols employed did not affect incidence of hyperthyroidism or anti-TSHR antibody titers in BALB/c mice. High-dose irradiation increased the relative ratios of effector T cells to regulatory T cells (an indication of enhanced immune status) but kills most of T cells.

Conclusions: These results indicate that a single whole-body low-dose irradiation with 0.5 Gy exacerbates thyroiditis in NOD-H2(h4) mice, data consistent with some clinical evidence for increased incidence of thyroid autoimmunity by environmental irradiation.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenoviridae / genetics
  • Animals
  • Antibodies / immunology
  • Disease Models, Animal
  • Female
  • Gene Expression Regulation, Viral
  • Graves Disease / immunology
  • Graves Disease / pathology
  • H-2 Antigens / immunology*
  • Hashimoto Disease / chemically induced
  • Hashimoto Disease / immunology
  • Hashimoto Disease / pathology
  • Humans
  • Immunization
  • Mice
  • Mice, Inbred NOD
  • Radiation Dosage*
  • Receptors, Thyrotropin / immunology
  • Receptors, Thyrotropin / metabolism
  • T-Lymphocytes / radiation effects
  • Thyroiditis, Autoimmune / immunology
  • Thyroiditis, Autoimmune / pathology*
  • Whole-Body Irradiation*

Substances

  • Antibodies
  • H-2 Antigens
  • Receptors, Thyrotropin