title: Pegylated G-CSF inhibits blood cell depletion, increases platelets, blocks splenomegaly, and improves survival after whole-body ionizing irradiation but not after irradiation combined with burn.
abstract: Exposure to ionizing radiation alone (radiation injury, RI) or combined with traumatic tissue injury (radiation combined injury, CI) is a crucial life-threatening factor in nuclear and radiological accidents. As demonstrated in animal models, CI results in greater mortality than RI. In our laboratory, we found that B6D2F1/J female mice exposed to (60)Co-γ-photon radiation followed by 15% total-body-surface-area skin burns experienced an increment of 18% higher mortality over a 30-day observation period compared to irradiation alone; that was accompanied by severe cytopenia, thrombopenia, erythropenia, and anemia. At the 30th day after injury, neutrophils, lymphocytes, and platelets still remained very low in surviving RI and CI mice. In contrast, their RBC, hemoglobin, and hematocrit were similar to basal levels. Comparing CI and RI mice, only RI induced splenomegaly. Both RI and CI resulted in bone marrow cell depletion. It was observed that only the RI mice treated with pegylated G-CSF after RI resulted in 100% survival over the 30-day period, and pegylated G-CSF mitigated RI-induced body-weight loss and depletion of WBC and platelets. Peg-G-CSF treatment sustained RBC balance, hemoglobin levels, and hematocrits and inhibited splenomegaly after RI. The results suggest that pegylated G-CSF effectively sustained animal survival by mitigating radiation-induced cytopenia, thrombopenia, erythropenia, and anemia.
authors.affiliation: Radiation Combined Injury Program, Armed Forces Radiobiology Research Institute, Bethesda, MD 20889, USA ; Department of Radiation Biology, Uniformed Services University of the Health Sciences, Bethesda, MD 20814, USA ; Department of Medicine, Uniformed Services University of the Health Sciences, Bethesda, MD 20814, USA.
authors.forename: Juliann G
authors.initials: JG
authors.lastname: Kiang
authors.affiliation: Radiation Combined Injury Program, Armed Forces Radiobiology Research Institute, Bethesda, MD 20889, USA.
authors.forename: Min
authors.initials: M
authors.lastname: Zhai
authors.affiliation: Radiation Combined Injury Program, Armed Forces Radiobiology Research Institute, Bethesda, MD 20889, USA.
authors.forename: Pei-Jyun
authors.initials: PJ
authors.lastname: Liao
authors.affiliation: Radiation Combined Injury Program, Armed Forces Radiobiology Research Institute, Bethesda, MD 20889, USA.
authors.forename: David L
authors.initials: DL
authors.lastname: Bolduc
authors.affiliation: Radiation Combined Injury Program, Armed Forces Radiobiology Research Institute, Bethesda, MD 20889, USA.
authors.forename: Thomas B
authors.initials: TB
authors.lastname: Elliott
authors.affiliation: Radiation Combined Injury Program, Armed Forces Radiobiology Research Institute, Bethesda, MD 20889, USA.
authors.forename: Nikolai V
authors.initials: NV
authors.lastname: Gorbunov
mesh_terms: D000818:Animals; D001792:Blood Platelets / Q000187:drug effects / Q000473:pathology* / Q000528:radiation effects; D001835:Body Weight / Q000187:drug effects / Q000528:radiation effects; D001854:Bone Marrow Cells / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D002056:Burns / Q000097:blood / Q000150:complications* / Q000188:drug therapy; D002452:Cell Count; D005260:Female; D016179:Granulocyte Colony-Stimulating Factor / Q000494:pharmacology / Q000627:therapeutic use*; D051379:Mice; D009929:Organ Size / Q000187:drug effects; D011092:Polyethylene Glycols / Q000737:chemistry*; D011839:Radiation, Ionizing; D013154:Spleen / Q000187:drug effects / Q000473:pathology; D013163:Splenomegaly / Q000097:blood / Q000150:complications / Q000188:drug therapy*; D016019:Survival Analysis; D014916:Whole-Body Irradiation
chemical_list: D016179:Granulocyte Colony-Stimulating Factor; D011092:Polyethylene Glycols
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