Insulin-Like Growth Factor 1 Protects against Lethal Irradiation

Ionizing irradiation can cause bone marrow failure leading to death. Effective therapeutic agents capable of promoting or accelerating the recovery of the hematopoietic and/or immune compartment following radiation injury are limited. We and others have previously demonstrated that recombinant human growth hormone promotes hematopoietic and immune recovery following stem cell transplantation and irradiation. Published data suggest that growth hormone elicits its pro-hematopoietic effects via action of insulin-like growth factor 1 (IGF1). Since IGF1 has recently been approved by the Federal Drug Administration to treat other conditions, IGF1 could be brought to the clinic rapidly upon demonstration of its activity. In this study, we sought to determine whether IGF1 has radioprotective activity. The studies were performed using BALB/c mice. Recombinant human insulin-like growth factor 1 (rhIGF1) was administered at a dose of 100 mcg/dose, i.v., once a day, starting within one hour after irradiation. BALB/c mice were irradiated with 7.5 Gy and treated with saline or rhIGF1 for 5 days. In the saline control group, all mice (10 out of 10 mice) died within 25 days following irradiation. By contrast, four out of 10 mice (40%) in the rhIGF1-treated group survived more than 100 days after irradiation (Figure, P<0.01). These data indicate that rhIGF1 can protect against lethal irradiation. Because one of the primary causes of death following irradiation is infections, we next sought to determine the effects of rhIGF1 on immune recovery. Compared with the saline control group, treatment with rhIGF1 for 5 days on irradiated (7.5 Gy) BALB/c mice significantly accelerated the recovery of CD4 and CD8 T cell subsets, B cells, and NK cells following irradiation. Our data demonstrate that rhIGF1 could potentially serve as a medical countermeasure in radiation emergencies.

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