The potential relationship between the neuroendocrine system and hematopoiesis has been postulated for many years. Growth hormone, which is produced by the anterior pituitary, has been postulated to have 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 demonstrated safety profile of recombinant human growth hormone (HGH) in humans, make HGH an attractive candidate for application in the treatment of victims of ionizing radiation exposure, whose hematopoietic and immune systems can be rapidly and severely depleted. However, the activity of HGH toward stimulating the hematopoietic stem cell (HSC) compartment or the immune system following radiation injury has not been demonstrated.
The primary aim of this application is to characterize the activity of GH toward promoting the accelerated recovery of the hematopoietic and immune systems following radiation damage and to provide this known clinically available product for broad application in the setting of a nuclear attack or dirty bomb. HGH is an FDA-approved drug and is therefore more rapidly deliverable as a candidate radiotherapeutic product. Moreover, growth hormone protects human lymphocytes from irradiation induced cell death and our data demonstrates that growth hormone stimulates murine host immune reconstitution (phenotypically and functionally) following lethal dose total body irradiation.
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