Exacerbation of autoimmune thyroiditis by a single low dose of whole-body irradiation in non-obese diabetic-H2^h4mice

Abstract

Purpose: To evaluate how irradiation affects thyroid autoimmunity in mouse models of Hashimoto's thyroiditis and Graves' hyperthyroidism. 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. Materials and methods: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 3 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.4

Effects of Low-Dose-Gamma Rays on the Immune System of Different Animal Models of Disease

“…Nagayama et al(2008) showed that a single dose of whole-body γ-irradiation with 0.5Gy one week prior to beginning NaI significantly enhanced the severity of thyroiditis and titers of anti-Tg autoantibodies. They concluded that low-dose irradiation exacerbated thyroid autoimmunity in NOD-H2 h4 mice, as demonstrated by the elevated thyroiditis scores and anti-Tg autoantibody titers.…”

“…HT is considered to be an autoimmune disease and previous studies examined thyroid-related autoantibodies (Jasani et al 1999;Nakamura et al 2008). As significant correlations between irradiation and thyroid autoimmunity were observed in studies conducted at Chernobyl (Vykhovanets et al 1997;Pacini et al 1998), Nagayama et al (2008) attempted to evaluate how irradiation affected thyroid autoimmunity in a mouse model. They used a spontaneous model of non-obese diabetic-H2 h4 (NOD-H2 h4 ) mice for HT, which develop antithyrogloblin autoantibodies and intrathyroidal lymphocyte infiltration when supplied with iodine in their drinking water (Many et al 1996;Rasooly et al 1996).…”

“…The pathological severity of AD and asthma were not evaluated by histological examinations in our referenced three studies (Fang et al , 2006Nagayama et al 2008). They evaluated pathological exacerbation following low-dose irradiation based on cytokine levels and T-cell subpopulations.…”

“…6. Nagayama et al (2008) Fractionated whole-body irradiation with 0.05 Gy/mouse twice a week. Fractionated whole-body irradiation with 0.5 Gy/mouse once a week.…”

“…The results obtained from animal experiments demonstrated that low-dose whole-body irradiation enhanced the immune response by augmenting the proliferative reactive response of T cells to mitogenic stimulation (Kojima et al 2000a;Pandey et al 2005), altering cytokine release (Liu et al 2003;Cheda et al 2008) and immune cell populations (Ina and Sakai 2005), and/or augmenting T cell activation capacity by dendritic cells (Shigematsu et al 2007). Regarding autoimmunity, the potentiation of T cell-mediated immunity in autoimmune-prone mice following exposure to low-dose irradiation was examined at the end of the 20 th century (James and Makinodan 1988;James et al 1990), and several research groups subsequently focused on the effects of low-dose irradiation on autoimmune diseases such as systemic lupus erythematosus (Ootsuyama et al 2003;Tanaka et al 2005;Tago et al 2008), multiple sclerosis , rheumatoid arthritis (Nakatsukasa et al , 2010Weng et al 2010) and autoimmune thyroiditis (Nagayama et al 2008) after the start of the 21 st century. Some groups have also focused on the effects of low-dose irradiation on allergic diseases, such as asthma and atopic dermatitis (Fang et al 2006).…”