title: Role of radiation-induced granulocyte colony-stimulating factor in recovery from whole body gamma-irradiation.
abstract: The purpose of this study was to further elucidate the radioprotective role of granulocyte colony-stimulating factor (G-CSF) induced in response to irradiation. The induction of G-CSF and interleukin-6 (IL-6) in response to radiation exposure was evaluated in mice. The level of cytokine in serum was determined by multiplex Luminex. The role of G-CSF on survival and tissue injury after total body gamma-irradiation was evaluated by administration of neutralizing antibody to G-CSF before radiation exposure. An isotype control was used for comparison and survival was monitored for 30 d after irradiation. Jejunum samples were used for immunohistochemistry. Ionizing radiation exposure induced significant levels of the hematopoietic cytokines G-CSF and IL-6, in mice receiving 9.2 Gy radiation. Maximal levels of G-CSF were observed in peripheral blood of mice 8h after irradiation. IL-6 levels were maximum at 12h after irradiation. Administration of G-CSF antibody significantly enhanced mortality in irradiated mice. G-CSF antibody-treated mice had higher numbers of CD68(+) cells and apoptotic cells in intestinal villi. Our results confirm that radiation exposure induces elevations of circulating G-CSF and IL-6. Neutralizing antibody to G-CSF exacerbates the deleterious effects of radiation, indicating that G-CSF induced in response to irradiation plays an important role in recovery.
authors.affiliation: Radiation Countermeasures Program, Armed Forces Radiobiology Research Institute, Uniformed Services University of the Health Sciences, Bethesda, MD, USA. singh@afrri.usuhs.mil
authors.forename: Vijay K
authors.initials: VK
authors.lastname: Singh
authors.forename: Oluseyi O
authors.initials: OO
authors.lastname: Fatanmi
authors.forename: Pankaj K
authors.initials: PK
authors.lastname: Singh
authors.forename: Mark H
authors.initials: MH
authors.lastname: Whitnall
mesh_terms: D000818:Animals; D016179:Granulocyte Colony-Stimulating Factor / Q000096:biosynthesis / Q000502:physiology*; D007150:Immunohistochemistry; D020287:In Situ Nick-End Labeling; D015850:Interleukin-6 / Q000096:biosynthesis; D008297:Male; D051379:Mice; D014916:Whole-Body Irradiation
chemical_list: D015850:Interleukin-6; D016179:Granulocyte Colony-Stimulating Factor