Objective: To observe the radioprotection of recombinant human interleukin-3 (rhIL-3), granulocyte-macrophage colony-stimulating factor (GM-CSF) and rhIL-3 (rhIL-3+GM-CSF) on peripheral lymphocytes of rhesus monkey irradiated by 3.0 Gy gamma-rays, and attempt to provide evidence of cytokines used effectively in the therapy of acute radiation sickness.
Methods: Thirty rhesus monkey used in the experiment were randomly divided into six groups of rhIL-3 20 microg.kg -1.d -1, 60 microg.kg -1.d -1 GM-CSF 10 microg.kg -1.d -1 IL-3 20 microg.kg -1.d -1 +GM-CSF 10 microg.kg -1.d -1 radiation control and normal control. 21 d after whole body gamma-irradiation and subcutaneous injection of cytokines, T lymphocyte and its subsets, Bax/Bcl-2 proteins in lymphocytes were determined by immunohistochemical staining with alkaline phosphatase, and lymphocyte apoptosis was detected by TdT-mediated dUTP nick end labeling (TUNEL) technique.
Results: (1) After irradiation the quantities of peripheral lymphocyte, T cell and its subsets obviously decreased as compared with those of normal controls. For instance, the percentages of lymphocyte, T, T H and Ts cells in radiation control group reduced to 44 percent, 42 percent, 41 percent and 57 percent of normal controls, respectively. (2)After radiation the reduction of lymphocyte, T, T H and Ts cells were evidently improved by injection of GM-CSF and GM-CSF+IL-3, The T,T H cells in GM-CSF and GM-CSF+IL-3 groups were respectively elevated by 1.57 and 1.76 fold, as well as 1.48 and 1.72 fold of radiation controls. (3) A large amount of lymphocyte apoptosis was found after radiation, GM-CSF and GM-CSF+IL-3 treatment could distinctively inhibit abundant lymphocyte apoptosis induced by acute irradiation,the apoptotic rates of lymphocytes in GM-CSF and GM-CSF+IL-3 groups reduced to 41 percent and 48 percent respectively when compared with that of radiation controls.
Conclusion: A definite dose of GM-CSF and GM-CSF+IL-3 could suppress the reduction of lymphocyte, T and T H cells and lymphocyte apoptosis induced by 3.0 Gy gamma-irradiation. It confirms that inhibition of GM-CSF and GM-CSF+IL-3 on lymphocyte reduction as well as apoptosis might be one of the major causes to alleviate radiation injury of lymphocytes and improve the immunological function.