Therapeutic administration of recombinant human granulocyte colony-stimulating factor accelerates hemopoietic regeneration and enhances survival in a murine model of radiation-induced myelosuppression.
The primary cause of death after radiation exposure is infection resulting from myelosuppression. Because granulocytes play a critical role in host defense against infection and because granulocyte proliferation and differentiation are enhanced by granulocyte colony-stimulating factor (G-CSF), this agent was evaluated for the ability to accelerate hemopoietic regeneration and to enhance survival in irradiated mice. C3H/HeN mice were irradiated and G-CSF (2.5 micrograms/day, s.c.) or saline was administered on days 3-12, 1-12 or 0-12 post-irradiation. Bone marrow, splenic and peripheral blood cellularity, and bone marrow and splenic granulocyte-macrophage progenitor cell recoveries were evaluated in mice exposed to 6.5 Gy. Mice exposed to 8 Gy were evaluated for multipotent hemopoietic stem cell recovery (using endogenous spleen colony-forming units) and enhanced survival. Results demonstrated that therapeutic G-CSF 1) accelerates hemopoietic regeneration after radiation-induced myelosuppression, 2) enhances survival after potentially lethal irradiation and 3) is most effective when initiated 1 h following exposure.
Department of Experimental Hematology, Armed Forces Radiobiology Research Institute, Bethesda, Maryland 20814-5145.
M L
ML
Patchen
T J
TJ
MacVittie
B D
BD
Solberg
L M
LM
Souza
D000380:Agranulocytosis / Q000188:drug therapy*; D000741:Anemia, Aplastic / Q000188:drug therapy* / Q000209:etiology; D000818:Animals; D003114:Colony-Forming Units Assay; D003115:Colony-Stimulating Factors / Q000494:pharmacology / Q000627:therapeutic use*; D016179:Granulocyte Colony-Stimulating Factor; D006098:Granulocytes / Q000187:drug effects; D006410:Hematopoiesis / Q000187:drug effects; D006801:Humans; D007958:Leukocyte Count / Q000187:drug effects; D051379:Mice; D008809:Mice, Inbred C3H; D009503:Neutropenia / Q000188:drug therapy* / Q000209:etiology; D011833:Radiation Injuries, Experimental / Q000188:drug therapy* / Q000209:etiology; D011994:Recombinant Proteins / Q000627:therapeutic use; D015996:Survival Rate; D014916:Whole-Body Irradiation / Q000009:adverse effects
D003115:Colony-Stimulating Factors; D011994:Recombinant Proteins; D016179:Granulocyte Colony-Stimulating Factor