title: [Therapeutic Effect of Combined Cytokines on Nonhuman Primate Model of Severe Haemopoietic Acute Radiation Sickness].
abstract: OBJECTIVE
  To evaluate the therapeutic effects of combined administration of recombinant human granulocyte colony-stimulating factor (rhG-CSF), recombinant human thrombopoietin (rhTPO) and recombinant human interleukin-2 (rhIL-2) on radiation-induced severe haemopoietic acute radiation sickness (ARS) in rhesus monkeys, so as to provide experimental evidences for the effective clinical treatment.
  
  
  METHODS
  Seventeen rhesus monkeys were exposed to 7.0 Gy (60)Co γ-ray total body irradiation (TBI) to establish severe haemopoietic ARS model, and were randomly divided into supportive care group, rhG-CSF+rhTPO treatment group and rhG-CSF+rhTPO+rhIL-2 treatment group. Survival time, general signs such as bleeding and infections, and peripheral blood cell counts in each group were monitored. Bone marrow cells were cultivated to examine the colony formation ability. The histomorphology changes of bone marrow were observed at 45 d post irradiation.
  
  
  RESULTS
  After 7.0 Gy (60)Co γ-ray TBI, monkeys of supportive care group underwent tarry stool and emesis, then died in 12~18 d. The overall survival rate in this group was 16.7%. Gastrointestinal reactions of monkeys in two combined-cytokines treatment groups were inapparent. Combined-cytokines treatment induced 100% survival. Complete blood cells declined sharply after irradiation in each group, but two combined-cytokines treatment schemes could elevate the nadir of all blood cells, shorten the duration of pancytopenia and accelerate the recovery of hemogram. Compared with rhG-CSF+ rhTPO treatment, rhG-CSF+ rhTPO+ rhIL-2 treatment could increase the counts of lymphocytes and monocytes. The colony-formation rate of haemopoietic stem/progenitor cells in bone marrow dropped markedly at 2 d after irradiation. Combined-cytokines treatment promoted the ability of colony formation on day 29. Hematopoietic cells mostly disappeared in bone marrow of animals in supportive care group, but hematopoietic functions were recovered after cytokines were administrated.
  
  
  CONCLUSIONS
  rhG-CSF+ rhTPO and rhG-CSF+ rhTPO+ rhIL-2 treatment can significantly promote hematopoiesis recovery, improve the quantity of life, simplify the supportive therapy, and enhance the survival rate of rhesus monkeys with severe haemopoietic ARS induced by 7.0 Gy (60)Co γ-ray exposure. Especially the application of rhIL-2 can accelerate the recovery of lymphocytes and monocytes and restore the immunological function. Thus, combination of rhG-CSF, rhTPO and rhIL-2 on the basis of supportive care is an efficient strategy to treat severe haemopoietic ARS.
authors.affiliation: Medical College of Soochow University, Suzhou 215006, Jiangsu Province, China.
authors.forename: Yan-Chao
authors.initials: YC
authors.lastname: Ma
authors.affiliation: Medical College of Soochow University, Suzhou 215006, Jiangsu Province, China.
authors.forename: Ming
authors.initials: M
authors.lastname: Li
authors.affiliation: Institute of Radiation Medicine, Academy of Military Medical Sciences, Beijing 100850, China.
authors.forename: Shuang
authors.initials: S
authors.lastname: Xing
authors.affiliation: Institute of Radiation Medicine, Academy of Military Medical Sciences, Beijing 100850, China.
authors.forename: Guo-Lin
authors.initials: GL
authors.lastname: Xiong
authors.affiliation: Institute of Radiation Medicine, Academy of Military Medical Sciences, Beijing 100850, China.
authors.forename: Xing
authors.initials: X
authors.lastname: Shen
authors.affiliation: Medical College of Soochow University, Suzhou 215006, Jiangsu Province, China.
authors.forename: Qiu
authors.initials: Q
authors.lastname: Chen
authors.affiliation: Institute of Radiation Medicine, Academy of Military Medical Sciences, Beijing 100850, China.
authors.forename: Yu-Wen
authors.initials: YW
authors.lastname: Cong
authors.affiliation: Medical College of Soochow University, Suzhou 215006, Jiangsu Province, China.
authors.forename: Jin-Xiang
authors.initials: JX
authors.lastname: Wang
authors.affiliation: Medical College of Soochow University, Suzhou 215006, Jiangsu Province, China.
authors.forename: Nan-Kang
authors.initials: NK
authors.lastname: Zhu
authors.affiliation: Institute of Radiation Medicine, Academy of Military Medical Sciences, Beijing 100850, China. E-mail: yuzy79@163.com.
authors.forename: Zu-Yin
authors.initials: ZY
authors.lastname: Yu
authors.affiliation: Medical College of Soochow University, Suzhou 215006, Jiangsu Province, China. E-mail: xueguangzh@126.com.
authors.forename: Xue-Guang
authors.initials: XG
authors.lastname: Zhang
mesh_terms: D000818:Animals; D001853:Bone Marrow / Q000473:pathology; D001854:Bone Marrow Cells / Q000473:pathology; D005720:Gamma Rays; D016179:Granulocyte Colony-Stimulating Factor / Q000494:pharmacology*; D006410:Hematopoiesis / Q000187:drug effects*; D006412:Hematopoietic Stem Cells / Q000166:cytology; D006801:Humans; D007376:Interleukin-2 / Q000494:pharmacology*; D008253:Macaca mulatta; D011832:Radiation Injuries / Q000188:drug therapy*; D011897:Random Allocation; D011994:Recombinant Proteins / Q000627:therapeutic use; D013926:Thrombopoietin / Q000494:pharmacology*; D014916:Whole-Body Irradiation
chemical_list: D007376:Interleukin-2; D011994:Recombinant Proteins; D016179:Granulocyte Colony-Stimulating Factor; D013926:Thrombopoietin