Haematological effects of rhGM-CSF in dogs exposed to total-body irradiation with a dose of 2.4 Gy.
It was the specific aim of this study to test the stimulatory effects of recombinant human GM-CSF (rhGM-CSF) on haemopoietic regeneration in dogs which had received total-body irradiation (TBI) with a dose of 2.4 Gy. In normal dogs rhGM-CSF given subcutaneously at 10 microgram/kg per day or 30 microgram/kg per day for 21 days caused strong but transient increases in the peripheral blood neutrophils. The monocyte counts also showed a transient rise during treatment in a dose-dependent fashion, whereas the lymphocyte counts increased only at the higher dose of rhGM-CSF and the platelet counts were transiently depressed during the course of the treatment. In the irradiated animals treatment with rhGM-CSF decreased the severity and shortened the duration of neutropenia but had no significant influence on monocyte or lymphocyte recovery. The granulocyte values showed a characteristic pattern of fluctuations with the first peak occurring at the same time (day 10 to day 13) when the abortive rise was observed in the untreated dogs. In contrast the GM-CFC in the peripheral blood remained depressed during the whole treatment course, similar to the untreated irradiated controls. These results indicate that treatment with GM-CSF can be an effective biological monotherapy for radiation-induced bone marrow failure, but that for higher radiation doses the number of GM-CSF responsive target cells will become a critical determinant of therapeutic efficacy.
Institute of Occupational and Social Medicine, University of Ulm, Federal Republic of Germany.
W
W
Nothdurft
C
C
Selig
T M
TM
Fliedner
P
P
Hintz-Obertreis
L
L
Kreja
D
D
Krumwieh
R
R
Kurrle
F R
FR
Seiler
W
W
Weinsheimer
D000818:Animals; D004285:Dogs; D005260:Female; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000627:therapeutic use*; D006412:Hematopoietic Stem Cells / Q000187:drug effects / Q000502:physiology* / Q000528:radiation effects; D008297:Male; D011833:Radiation Injuries, Experimental / Q000628:therapy*; D011994:Recombinant Proteins; D012038:Regeneration / Q000187:drug effects* / Q000502:physiology; D014916:Whole-Body Irradiation
D011994:Recombinant Proteins; D016178:Granulocyte-Macrophage Colony-Stimulating Factor