Purpose: We already reported that levels of interferon (IFN)-γ have been shown to be markedly reduced in mice seven weeks after irradiation, resulting in a T helper (Th) 1/Th2 imbalance. To investigate whether the single or fractionated γ-irradiation induced an immune imbalance, we analysed the Th1-related immune response profile until six months after the fractionated whole-body irradiation.
Methods and materials: Mice were exposed to γ-rays at a fractionated 5 Gy cumulative dose for five weeks. At two, four and six months later from the first exposure, experiments were performed. Cell populations in the spleen, the production of IFN-γ, interleukin (IL)- 4 and IL-12p70, natural killer (NK) cell activity and the expression of IL-12 receptors, signal transducer and activator of transcription (STAT) 4 and suppressors of cytokine signaling (SOCS) 3 were detected.
Results: The IFN-γ was lower in the mice exposed by all irradiation conditions than in normal control mice, but the IL-4 had increased in all the irradiated mice. To investigate Th1 profile, NK cell activity, IL-12p70 level and its receptor expression was confirmed. In all fractionated irradiation groups, the NK cell activity as well as the absolute numbers of NK cells was much decreased. Also, all the irradiated mice showed a lower IL-12p70 level. However, the expression of IL-12 receptor β2 was lower in the irradiated mice except the 0.2 Gy × 10 mice group. The phosphoylated STAT4 was lower in all the irradiated mice. This suppression was associated with an overexpression of SOCS3.
Conclusions: The fractionated whole-body irradiations of a dose of 5 Gy appear to be the down-regulation of the Th1-like immune response. These changes, in turn, maintain an immunological imbalance that persists in the long term.