Effect of Repeated Small-Dose .GAMMA.-Ray Irradiation on Atopic Dermatitis in NC/Nga Mice

Abstract

We previously showed that several small-dose 0.5 Gy whole-body γ-ray irradiation inhibits tumor growth in mice via elevation of the interferon (IFN)-γ/interleukin 4 (IL-4) ratio concomitantly with a decrease in the percentage of B cells. Here, we examined whether repeated small-dose (0.5 Gy, 10 times) γ-ray irradiation influences atopic dermatitis in an NC/Nga mouse model. It was found that repeated γ-ray irradiation increased total IgE in comparison with the disease-control group. Levels of IL-4 and IL-5 were increased versus the disease-control group, while IFN-γ was slightly decreased, resulting in a further decrease of the IFN-γ/IL-4 ratio compared with the disease-control group. These results indicate that repeated small-dose γ-ray irradiation may exacerbate atopic dermatitis. This may be because the irradiation induces not helper T lymphocyte 1 (Th1), but Th2 polarization in this atopic mouse model, i.e., the effects of small-dose irradiation may be different in conditions involving immune hypersensitivity and impaired immunity.

Therapeutic Effects of Gyokuheifusan on NC/Nga Mouse Model of Allergic Dermatitis

“…The levels of cytokines (IFN-γ, IL-4 and IL-5) in the culture supernatant were measured by ELISA. ELISA Procedures --Production of total IgE, IgG1, IgG2a and cytokines (IFN-γ, IL-4 and IL-5) was measured by ELISA using appropriate antibodies as described by Fang et al 19) Briefly, flatbottomed 96-well Maxisorp plates were coated with purified capture IgE mAb, IFN-γ mAb, IL-4 mAb or IL-5 mAb overnight at 4 • C. The primary mAbs were discarded and the plates were blocked with blocking buffer [1% bovine serum albumin (BSA) in phosphate-buffered saline (PBS)] for 1 hr at room temperature, then washed 3 times with wash buffer (0.05% Tween 20 in PBS). Appropriately diluted samples or IgE, IFN-γ, IL-4 and IL-5 standards were added and the plates were incubated for 2 hr at room temperature.…”

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

“…These anti-tumor effects were mediated by radiation-induced elevations in the IFN-γ / IL-4 (type1-helper (Th-1) cytokine / Th-2 cytokine) ratio. Fang et al (2006) considered that such cytokine polarization may also contribute to the treatment of AD. NC/Nga mice, which were established as an inbred strain by Kondo in 1957 based on Japanese fancy mice, were shown to be suitable as an animal model of AD (Kondo et al 1969;Festing 1996), and were subsequently treated with a mite antigen.…”

“…This animal model was shown to manifest clinical and immunological aspects similar to patients with AD (Sasakawa et al 2001). Fang et al (2006) attempted to induce AD models in NC/Nga mice, which were irradiated with 0.5 Gy of γ-rays 2 days before each stimulation with the mite antigen, twice a week from the age of 7 to 11 weeks old (total 10 times) (Fig. 4).…”

“…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). These studies originated from the proposal that low-dose irradiation could alter cytokine levels and the percentage of T cell subpopulations, which may in turn contribute to the attenuation of pathologies.…”

Immunomodulatory effects of ultraviolet B irradiation on atopic dermatitis in NC/Nga mice

“…We previously examined the effect of repeated low‐dose 0.5 Gy γ‐ray irradiation on AD in NC/Nga mice (27). The irradiation increased the levels of IgE, IL‐4, and IL‐5, suggesting that repeated low‐dose γ‐ray irradiation may exacerbate atopic dermatitis.…”