Medical countermeasures for radiation combined injury: radiation with burn, blast, trauma and/or sepsis. report of an NIAID Workshop, March 26-27, 2007

Abstract

Non-clinical human radiation exposure events such as the Hiroshima and Nagasaki bombings or the Chernobyl accident are often coupled with other forms of injury, such as wounds, burns, blunt trauma, and infection. Radiation combined injury would also be expected after a radiological or nuclear attack. Few animal models of radiation combined injury exist, and mechanisms underlying the high mortality associated with complex radiation injuries are poorly understood. Medical countermeasures are currently available for management of the non-radiation components of radiation combined injury, but it is not known whether treatments for other insults will be effective when the injury is combined with radiation exposure. Further research is needed to elucidate mechanisms behind the synergistic lethality of radiation combined injury and to identify targets for medical countermeasures. To address these issues, the National Institute of Allergy and Infectious Diseases convened a workshop to make recommendations on the development of animal models of radiation combined injury, possible mechanisms of radiation combined injury, and future directions for countermeasure research, including target identification and end points to evaluate treatment efficacy.

FIG. 1.

The LD_50/30 for γ radiation is decreased by burn or skin-wound trauma in the mouse. Figure provided by G. D. Ledney, AFRRI, Bethesda, MD, as published in ref. (18).

FIG. 2.

Model showing how interactions between epithelial and endothelial radiation injury in the intestine causes endothelial dysfunction, exacerbates acute intestinal radiation toxicity, and subsequently sustains the cycle of chronicity of intestinal radiation fibrosis. Figure provided by M. Hauer-Jensen, from ref. (39) with permission from Nova Science Publishers, Inc.

FIG. 3.

Radiation exposure decreases the survival of mice injected with 1.1 × 10⁵ Klebsiella pneumoniae (K.p.) cells. Figure provided by T. Pellmar, AFRRI, Bethesda, MD (T. B. Elliott, unpublished data).