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 µg/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.
Highlights
The misuse of ionizing radiation or nuclear devices as weapons of terrorism has been recognized as a major public health threat [1,2]
BALB/c mice were whole-body irradiated with 7.5 Gy and treated with recombinant human growth hormone (rhGH) intravenously once daily at a dose of 20 mg/dose/day for 35 days starting within one hour post radiation exposure
Published data have demonstrated that rhGH enhances hematologic engraftment and immune recovery post hematopoietic stem cell transplantation [12,21]
Summary
The misuse of ionizing radiation or nuclear devices as weapons of terrorism has been recognized as a major public health threat [1,2]. Depending on the type of nuclear device, these casualties may range from trivial biological exposures ( causing severe anxiety) to acute high-dose exposures that result in the development of severe radiation sickness and death. Individuals exposed to ionizing radiation doses in the range of 0.7 to 4 Gy will develop symptoms that are secondary to hematopoietic and immune damage [3]. The majority of deaths that occur from exposures of 4–10 Gy result, in a large part, from the sequelae of hematopoietic and immune failure (bleeding and infections). Even at levels of radiation exposure significantly lower than those needed to cause symptoms of radiation sickness, there are alterations of the immune system so that the virulence and infectivity of biological agents (bacteria, viruses and fungi) are dramatically increased [4,5]. Therapeutic agents capable of promoting or accelerating the recovery of the hematopoietic and/or immune compartments following radiation injury are limited [1,2,3]
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