Growth Hormone Mitigates against Lethal Irradiation and Enhances Hematologic and Immune Recovery in Mice and Nonhuman Primates

被引：48

作者：

Chen, Benny J. ^{[1
]}

Deoliveira, Divino ^{[1
]}

Spasojevic, Ivan ^{[1
]}

Sempowski, Gregory D. ^{[1
,2
,5
]}

Jiang, Chen ^{[6
]}

Owzar, Kouros ^{[3
,6
]}

Wang, Xiaojuan ^{[1
]}

Gesty-Palmer, Diane ^{[1
]}

Cline, J. Mark ^{[7
]}

Bourland, J. Daniel ^{[8
]}

Dugan, Greg ^{[7
]}

Meadows, Sarah K. ^{[1
]}

Daher, Pamela ^{[1
]}

Muramoto, Garrett ^{[1
]}

Chute, John P. ^{[1
]}

Chao, Nelson J. ^{[1
,4
]}

机构：

[1] Duke Univ, Med Ctr, Dept Med, Durham, NC 27710 USA

[2] Duke Univ, Med Ctr, Dept Pathol, Durham, NC 27710 USA

[3] Duke Univ, Med Ctr, Dept Biostat & Bioinformat, Durham, NC USA

[4] Duke Univ, Med Ctr, Dept Immunol, Durham, NC USA

[5] Duke Univ, Med Ctr, Human Vaccine Inst, Durham, NC USA

[6] Duke Univ, Med Ctr, RadCCORE Biostat Core, Durham, NC USA

[7] Wake Forest Univ, Bowman Gray Sch Med, Comparat Med Sect, Winston Salem, NC USA

[8] Wake Forest Univ, Bowman Gray Sch Med, Dept Radiat Oncol, Winston Salem, NC USA

来源：

PLOS ONE | 2010年 / 5卷 / 06期

基金：

美国国家卫生研究院;

关键词：

COLONY-STIMULATING FACTOR; TUMOR NECROSIS FACTOR; T-CELL DEVELOPMENT; FACTOR-I; HEMATOPOIETIC STEM; NEUROENDOCRINE HORMONES; ERYTHROPOIESIS INVITRO; IONIZING-RADIATION; PROGENITOR CELLS; BONE-MARROW;

D O I：

10.1371/journal.pone.0011056

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

070301 [无机化学]; 070403 [天体物理学]; 070507 [自然资源与国土空间规划学]; 090105 [作物生产系统与生态工程];

摘要：

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 mu g/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.

引用

页数：12

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