title: Involvement of bystander effect in suppression of the cytokine production induced by heavy-ion broad beams.
abstract: OBJECTIVE
  Immune cells accumulate in and around cancers and cooperate with each other using specific cytokines to attack the cancer cells. The heavy-ion beams for cancer therapy may stimulate immune cells and affect on the immune system. However, it is still poorly understood how the immune cells are stimulated by ion-beams. Here, we irradiated immune cells using heavy-ion beams and analyzed changes in production of tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6) that are important cytokine for the cancer treatment.
  
  
  METHODS
  The human THP-1 monocytes were differentiated into macrophages and then irradiated using carbon-ion broad-beams (108 keV μm(-1)). To examine the bystander response after heavy-ion irradiation, a very small fraction (approx. 0.45%) of the cell population was irradiated using heavy-ion microbeams. After irradiation, we examined the cytokine productions.
  
  
  RESULTS
  When cells were irradiated with 5 Gy, cytokine levels were reduced after both microbeam irradiation and broad-beam irradiation. TNF-α production of macrophages with the nitric oxide (NO) inhibitor-treatment increased after carbon-ion broad-beam. NO was involved in the radiation-induced suppression of TNF-α production.
  
  
  CONCLUSIONS
  The suppression of cytokine production arose after irradiation with heavy-ions, and may also be induced in the surrounding non-irradiated cells via the bystander effect.
authors: Microbeam Radiation Biology Group, Quantum Beam Science Directorate, Japan Atomic Energy Agency, 1233 Watanuki, Takasaki, Gunma 370-1292, Japan.
authors: Yasuko
authors: Y
authors: Mutou-Yoshihara
authors: Tomoo
authors: T
authors: Funayama
authors: Yuichiro
authors: Y
authors: Yokota
authors: Yasuhiko
authors: Y
authors: Kobayashi
mesh_terms: D024201:Bystander Effect / Q000187:drug effects / Q000528:radiation effects*; D002244:Carbon / Q000009:adverse effects; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects / Q000528:radiation effects; D016207:Cytokines / Q000096:biosynthesis*; D020450:Heavy Ions / Q000009:adverse effects*; D006801:Humans; D007371:Interferon-gamma / Q000494:pharmacology; D015850:Interleukin-6 / Q000378:metabolism; D008070:Lipopolysaccharides / Q000494:pharmacology; D008264:Macrophages / Q000187:drug effects / Q000276:immunology / Q000378:metabolism / Q000528:radiation effects; D009569:Nitric Oxide / Q000037:antagonists & inhibitors; D009573:Nitrites / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
chemical_list: D016207:Cytokines; D015850:Interleukin-6; D008070:Lipopolysaccharides; D009573:Nitrites; D014409:Tumor Necrosis Factor-alpha; D009569:Nitric Oxide; D002244:Carbon; D007371:Interferon-gamma