Role of radiation-induced granulocyte colony-stimulating factor in recovery from whole body gamma-irradiation

• Published in: Cytokine (Philadelphia, Pa.) Vol. 58; no. 3; pp. 406 - 414
• Main Authors: Singh, Vijay K., Fatanmi, Oluseyi O., Singh, Pankaj K., Whitnall, Mark H.
• Format: Journal Article
• Language: English
• Published: England Elsevier Ltd 01.06.2012
• Subjects: Animals; Antibodies; Apoptosis; blood serum; Cytokines; G-CSF; gamma Radiation; Granulocyte colony-stimulating factor; Granulocyte Colony-Stimulating Factor - biosynthesis; Granulocyte Colony-Stimulating Factor - physiology; Hemopoiesis; Immunohistochemistry; In Situ Nick-End Labeling; Injuries; Interleukin 6; Interleukin-6 - biosynthesis; Intestine; Ionizing radiation; irradiation; Jejunum; Male; Mice; Mortality; Neutralization; neutralizing antibodies; Peripheral blood; Radiation; Survival; villi; Whole-Body Irradiation; Immunohistochemistry; Mice; Cytokines; G-CSF; Radiation; Neutralization
• ISSN: 1043-4666; 1096-0023
• DOI: 10.1016/j.cyto.2012.03.011

► We demonstrate that G-CSF plays an important role in the recovery from irradiation. ► Irradiation induces G-CSF and other hematopoietic cytokines such as interleukin-6. ► Administration of G-CSF antibody increased mortality in irradiated mice. ► G-CSF antibody administration also exacerbated radiation-induced tissue injury. 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 30d 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 9.2Gy 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.