Acute radiation syndrome (ARS) – treatment of the reduced host defense

Lars Heslet¹, Christiane Bay², Steen Nepper-Christensen<sup>3

1</sup>Serendex ApS, Gentofte; ²University of Copenhagen, Medical Faculty, Copenhagen; ³Department of Head and Neck Surgery, Otorhinolaryngology, Køge University Hospital, Køge, Denmark

Background: The current radiation threat from the Fukushima power plant accident has prompted rethinking of the contingency plan for prophylaxis and treatment of the acute radiation syndrome (ARS). The well-documented effect of the growth factors (granulocyte colony-stimulating factor [G-CSF] and granulocyte-macrophage colony-stimulating factor [GM-CSF]) in acute radiation injury has become standard treatment for ARS in the United States, based on the fact that growth factors increase number and functions of both macrophages and granulocytes.
Methods: Review of the current literature.
Results: The lungs have their own host defense system, based on alveolar macrophages. After radiation exposure to the lungs, resting macrophages can no longer be transformed, not even during systemic administration of growth factors because G-CSF/GM-CSF does not penetrate the alveoli. Under normal circumstances, locally-produced GM-CSF receptors transform resting macrophages into fully immunocompetent dendritic cells in the sealed-off pulmonary compartment. However, GM-CSF is not expressed in radiation injured tissue due to defervescence of the macrophages. In order to maintain the macrophage’s important role in host defense after radiation exposure, it is hypothesized that it is necessary to administer the drug exogenously in order to uphold the barrier against exogenous and endogenous infections and possibly prevent the potentially lethal systemic infection, which is the main cause of death in ARS.
Recommendation: Preemptive treatment should be initiated after suspected exposure of a radiation dose of at least ~2 Gy by prompt dosing of 250–400 µg GM-CSF/m² or 5 µg/kg G-CSF administered systemically and concomitant inhalation of GM-CSF ~ 300 mcg per day for at least 14–21 days.
Conclusion: The present United States standard for prevention and treatment of ARS standard intervention should consequently be modified into the combined systemic administration of growth factors and inhaled GM-CSF to ensure the sustained systemic and pulmonary host defense and thus prevent pulmonary dysfunction.

Keywords: inhaled and systemically administered GM-CSF, ARS, host defense, orchestration of pulmonary host response