Revisiting therapeutic strategies in radiation casualties.
OBJECTIVE
Nuclear/radiological threats have evolved and scenarios for terrorist attacks involving radioactive material have been identified as complex situations. Mass casualty scenarios may happen, and individuals may be exposed to intentionally hidden sources of high activity, resulting in delayed diagnosis and treatment of acute radiation syndrome (ARS). Moreover, ARS must be considered as an emergency in order to better anticipate delayed radiation toxicity. In this context, therapeutic strategies in radiation casualties have to be revisited and new pharmacological approaches developed.


METHODS
B6D2F1 mice were total-body irradiated (TBI) with a 9 Gy gamma dose and then received intraperitoneal doses of either early (stem cell factor + FLT-3 ligand + thrombopoietin + interleukin-3 [SFT3] +/- keratinocyte growth factor (KGF); stem cell factor + erythropoietin + Peg-filgrastim [SEG]) or delayed treatments (SFT3 +/- KGF, erythropoietin, or hyaluronic acid). Survival was monitored and bone marrow hematopoiesis evaluated at 300 days following early treatments.


RESULTS
SFT3 anti-apoptotic cytokine combination administered early (2 hours and 24 hours) after lethal TBI induced 60% survival versus 5% in controls. Early SEG treatment may be an alternative to SFT3 in terms of survival (55%), but SEG benefit might be obtained at the expense of long-term hematopoiesis. SFT3 + KGF induced 75% survival. No effectiveness was observed, over antimicrobial supportive care, when administration of SFT3 or its tested combinations was delayed at 48 hours.


CONCLUSIONS
As a potentially multi-organ failure, ARS requires global therapy, beyond the hematopoietic syndrome, which may include pleiotropic cytokines such as KGF.
Hérodin
Francis
F
Centre de Recherches du Service de Santé des Armées, La Tronche, France. fherodin@crssa.net
Grenier
Nancy
N
Drouet
Michel
M
D000818:Animals; D004359:Drug Therapy, Combination; D005260:Female; D005720:Gamma Rays; D006133:Growth Substances / Q000494:pharmacology* / Q000627:therapeutic use; D006801:Humans; D051379:Mice; D011832:Radiation Injuries / Q000188:drug therapy* / Q000401:mortality; D018788:Radioactive Hazard Release / Q000401:mortality; D023481:Terrorism; D013997:Time Factors; D016896:Treatment Outcome; D014916:Whole-Body Irradiation
D006133:Growth Substances