Antiapoptotic cytokines in combination with pegfilgrastim soon after irradiation mitigates myelosuppression in nonhuman primates exposed to high irradiation dose

Details

Serval ID
serval:BIB_DCC24C9554C1
Type
Article: article from journal or magazin.
Collection
Publications
Title
Antiapoptotic cytokines in combination with pegfilgrastim soon after irradiation mitigates myelosuppression in nonhuman primates exposed to high irradiation dose
Journal
Exp Hematol
Author(s)
Herodin F., Roy L., Grenier N., Delaunay C., Bauge S., Vaurijoux A., Gregoire E., Martin C., Alonso A., Mayol J. F., Drouet M.
ISSN
0301-472X (Print)
ISSN-L
0301-472X
Publication state
Published
Issued date
08/2007
Volume
35
Number
8
Pages
1172-81
Language
english
Notes
Herodin, Francis
Roy, Laurence
Grenier, Nancy
Delaunay, Christophe
Bauge, Stephane
Vaurijoux, Aurelie
Gregoire, Eric
Martin, Cecile
Alonso, Antonia
Mayol, Jean-Francois
Drouet, Michel
eng
Research Support, Non-U.S. Gov't
Netherlands
2007/06/15
Exp Hematol. 2007 Aug;35(8):1172-81. doi: 10.1016/j.exphem.2007.04.017. Epub 2007 Jun 8.
Abstract
OBJECTIVE: Preservation of hematopoietic stem and progenitor cells from early radiation-induced apoptosis is the rationale for emergency antiapoptotic cytokine therapy (EACK) after radiation accidents. This strategy is based on the combination of stem cell factor + Flt3-ligand + thrombopoietin + interleukin 3 (SFT3). The long-term safety and efficacy of EACK in managing severe radiation exposure were evaluated. MATERIAL AND METHODS: Early administration of SFT3 + pegfilgrastim was assessed in 7-Gy gamma total body-irradiated (TBI) monkeys. Efficiency of delayed administration was also addressed after 5-Gy TBI. RESULTS: Here we showed that a single, intravenous injection of SFT3 2 hours after 7-Gy TBI reduced the period of thrombocytopenia (platelet count <20 x 10(9)/L: 0.8 +/- 1.5 day vs 23.8 +/- 15.9 days in controls; p < 0.05) and blood transfusion needs. Moreover, addition of pegfilgrastim to SFT3 treatment shortened the period of neutropenia compared with SFT3 and control groups (neutrophil count <0.5 x 10(9)/L: 7 +/- 1.4 days vs 13 +/- 3.2 days and 15.2 +/- 1.5 days; p < 0.05). In both SFT3 groups, bone marrow activity recovered earlier and, in contrast with controls, platelet count returned to baseline values from 250 days after irradiation. Furthermore, delayed (48 hours) single SFT3 administration in 5-Gy irradiated monkeys significantly reduced thrombocytopenia compared to controls. Finally, SFT3 did not increase frequency of total chromosome translocations observed in the blood lymphocytes of controls 1 year after 5 Gy TBI. CONCLUSION: These results suggest the safety and efficacy of EACK in managing severe radiation exposure.
Keywords
Animals, Apoptosis/*physiology/radiation effects, Blood Platelets/drug effects/radiation effects, Bone Marrow/drug effects/radiation effects, Chromosome Aberrations/*radiation effects, Cytokines/*pharmacology, Dose-Response Relationship, Radiation, Filgrastim, Granulocyte Colony-Stimulating Factor/*pharmacology, Hematopoiesis/*drug effects/radiation effects, Humans, Inflammation/physiopathology, Leukocytes/drug effects/radiation effects, Lymphocytes/cytology/drug effects/physiology/radiation effects, Macaca fascicularis, Male, Polyethylene Glycols, Recombinant Proteins/pharmacology
Pubmed
Create date
02/05/2024 9:41
Last modification date
28/05/2024 6:10
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