title: Growth hormone mitigates against lethal irradiation and enhances hematologic and immune recovery in mice and nonhuman primates.
abstract: Medications that can mitigate against radiation injury are limited. In this study, we investigated the ability of recombinant human growth hormone (rhGH) to mitigate against radiation injury in mice and nonhuman primates. BALB/c mice were irradiated with 7.5 Gy and treated post-irradiation with rhGH intravenously at a once daily dose of 20 microg/dose for 35 days. rhGH protected 17 out of 28 mice (60.7%) from lethal irradiation while only 3 out of 28 mice (10.7%) survived in the saline control group. A shorter course of 5 days of rhGH post-irradiation produced similar results. Compared with the saline control group, treatment with rhGH on irradiated BALB/c mice significantly accelerated overall hematopoietic recovery. Specifically, the recovery of total white cells, CD4 and CD8 T cell subsets, B cells, NK cells and especially platelets post radiation exposure were significantly accelerated in the rhGH-treated mice. Moreover, treatment with rhGH increased the frequency of hematopoietic stem/progenitor cells as measured by flow cytometry and colony forming unit assays in bone marrow harvested at day 14 after irradiation, suggesting the effects of rhGH are at the hematopoietic stem/progenitor level. rhGH mediated the hematopoietic effects primarily through their niches. Similar data with rhGH were also observed following 2 Gy sublethal irradiation of nonhuman primates. Our data demonstrate that rhGH promotes hematopoietic engraftment and immune recovery post the exposure of ionizing radiation and mitigates against the mortality from lethal irradiation even when administered after exposure.
authors.affiliation: Department of Medicine, Duke University Medical Center, Durham, North Carolina, United States of America. chen0032@mc.duke.edu
authors.forename: Benny J
authors.initials: BJ
authors.lastname: Chen
authors.forename: Divino
authors.initials: D
authors.lastname: Deoliveira
authors.forename: Ivan
authors.initials: I
authors.lastname: Spasojevic
authors.forename: Gregory D
authors.initials: GD
authors.lastname: Sempowski
authors.forename: Chen
authors.initials: C
authors.lastname: Jiang
authors.forename: Kouros
authors.initials: K
authors.lastname: Owzar
authors.forename: Xiaojuan
authors.initials: X
authors.lastname: Wang
authors.forename: Diane
authors.initials: D
authors.lastname: Gesty-Palmer
authors.forename: J Mark
authors.initials: JM
authors.lastname: Cline
authors.forename: J Daniel
authors.initials: JD
authors.lastname: Bourland
authors.forename: Greg
authors.initials: G
authors.lastname: Dugan
authors.forename: Sarah K
authors.initials: SK
authors.lastname: Meadows
authors.forename: Pamela
authors.initials: P
authors.lastname: Daher
authors.forename: Garrett
authors.initials: G
authors.lastname: Muramoto
authors.forename: John P
authors.initials: JP
authors.lastname: Chute
authors.forename: Nelson J
authors.initials: NJ
authors.lastname: Chao
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D013006:Growth Hormone / Q000008:administration & dosage*; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D011323:Primates; D011833:Radiation Injuries, Experimental / Q000517:prevention & control*; D011994:Recombinant Proteins / Q000008:administration & dosage; D016176:T-Lymphocyte Subsets
chemical_list: D011994:Recombinant Proteins; D013006:Growth Hormone