Medications that can mitigate against radiation injury are limited. of total white cells, CD4 and CD8 T cell subsets, W 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 assessed 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 203737-94-4 manufacture mediated the hematopoietic effects primarily through their niches. Comparable 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 given after exposure. Introduction The misuse 203737-94-4 manufacture of ionizing radiation or nuclear devices as weapons of terrorism has been acknowledged as a major public health threat , . In the event of a nuclear detonation, terrorist radiological (at the.g., dirty) bomb, or attack on a nuclear power herb, casualties may be 203737-94-4 manufacture generated well outside the periphery of the lethal zone. Depending on the type of nuclear device, these casualties may range from trivial biological exposures (nonetheless causing severe stress) to acute high-dose exposures that result in the development of severe radiation sickness and death. Typically, individuals uncovered to ionizing radiation doses in the range of 0.7 to 4 Gy will develop symptoms that are secondary to hematopoietic and immune damage . At exposures approximating 4 Gy, it is usually estimated that 50% of individuals will die within 60 days unless there is usually medical intervention , . The majority of deaths that occur from exposures of 4C10 Gy also result, in a large part, from the sequelae of hematopoietic and immune failure (bleeding and infections). In addition, 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 brokers (bacteria, viruses and fungi) are dramatically increased , . A compromised immune system exacerbates the effects of infectious brokers, including other biological pathogens such as anthrax, and may preclude the use of vaccines. Unfortunately, therapeutic brokers capable of promoting or accelerating the recovery of the hematopoietic and/or immune compartments following radiation injury are limited , , . The potential relationship between the neuroendocrine system and hematopoiesis has been postulated for many years . Growth hormone, which is usually produced by the anterior pituitary, has been exhibited to have 203737-94-4 manufacture a stimulatory role in erythropoiesis ,  and granulopoiesis  either through direct effects or indirectly via the action of insulin-like growth factor 1 (IGF-1) , . Growth hormone also stimulates lymphocyte production in rodents and growth hormone replacement in hypophysectomized animals has been associated with recovery of thymic function , . These biologic features, along with its exhibited safety profile of recombinant human growth hormone (rhGH) in humans, make rhGH an attractive candidate for use in the treatment of victims of ionizing radiation exposure where one’s hematopoietic and immune systems can be Rabbit Polyclonal to Cytochrome P450 17A1 rapidly and severely depleted. In this study, we investigated the power of rhGH following lethal and sub-lethal irradiation and its effect on the reconstitution of hematologic and immune systems using both mouse and nonhuman primate models. The results indicate that rhGH enhances both hematologic engraftment and immune recovery and mitigates the mortality from lethal and non-lethal irradiation. These beneficial effects are 203737-94-4 manufacture a result of enhanced hematopoiesis after treatment with rhGH. rhGH augments hematopoiesis mainly through impacting hematopoietic niches. Results rhGH mitigates against lethal irradiation We first tested the ability of rhGH to mitigate against.