title: Chronic effects of single and fractionated γ-irradiation on an impairment of Th1-related immune response.
abstract: OBJECTIVE
  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
  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.
authors.affiliation: Radiation Research Division for Biotechnology, Advanced Radiation Technology Institute, Jeongeup Campus of Korea Atomic Energy Research Institute, 1266 Sinjeong-dong, Jeonbuk, Republic of Korea.
authors.forename: Hae-Ran
authors.initials: HR
authors.lastname: Park
authors.forename: Sung-Kee
authors.initials: SK
authors.lastname: Jo
authors.forename: Hyeon-Soo
authors.initials: HS
authors.lastname: Eom
mesh_terms: D000818:Animals; D004307:Dose-Response Relationship, Radiation; D005260:Female; D005720:Gamma Rays; D007107:Immune System; D018664:Interleukin-12 / Q000378:metabolism; D015847:Interleukin-4 / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D008954:Models, Biological; D050797:STAT4 Transcription Factor / Q000378:metabolism; D000071223:Suppressor of Cytokine Signaling 3 Protein; D050826:Suppressor of Cytokine Signaling Proteins / Q000378:metabolism; D018417:Th1 Cells / Q000378:metabolism* / Q000528:radiation effects*; D014916:Whole-Body Irradiation
chemical_list: D050797:STAT4 Transcription Factor; C491411:Socs3 protein, mouse; D000071223:Suppressor of Cytokine Signaling 3 Protein; D050826:Suppressor of Cytokine Signaling Proteins; D018664:Interleukin-12; D015847:Interleukin-4