Nuclear accidents or attacks inflict both radiation injury and trauma resulting in a combined injury. While, the extent of the combined injury varies depending on the location of the victim, history indicates that individuals that experience combined injury succumb more readily to their injuries and develop more severe post-injury complications than patients with a single form of injury. The mechanisms responsible for the poor prognosis of combined injury victims are not know. The development of an animal model to study the effects of combined injury on the immune system would significantly advance research addressing the immune complications of combined injury. Therefore, the first phase of this phased innovation project will be to develop a mouse model for combined injury by exploring the effects of differing doses of radiation exposure and burn injury on cells and mediators of the immune system. We will collect data on immunophysiological changes in mice that are induced by radiation, by burn injury, and by combined radiation with burn injury. Experiments will also determine the immune competence of combined injured mice by testing their ability to resist bacterial infections and sepsis. The second phase this project will use this mouse model for combined injury to test the efficacy of using hematopoietic growth factor or Toll-like receptor adjuvants to induce immune cell recovery and stronger host defenses against pathogens in injured mice. During this phase, we will also test whether using counter-inflammatory treatments might protect injured mice from the detrimental effects of radiation, burn, or combined injury on the immune system. The results of these studies will provide us and other investigators with a validated mouse model for radiation combined injury and will significantly advance our understanding of how combined injury disrupts immune system function. Moreover, the findings of experiments testing the efficacy of immune-enhancing or counter-inflammatory treatments will provide insight into which therapeutic intervention might be the most beneficial to combined injury victims.

Public Health Relevance

Nuclear accidents or attacks inflict radiation injury and trauma causing what is referred to as combined injury. Combined injury victims develop severe immune system failure, which makes them highly susceptible to dying of infections. This project will develop a mouse model for combined injury that will be used to advance our understanding of how combined injury affects the immune system and this new information will then be used to test the effectiveness of immune-enhancing drugs on their ability to restore normal immune system function in combined injury victims.

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Exploratory/Developmental Grants Phase II (R33)
Project #
5R33AI080565-05
Application #
8321044
Study Section
Special Emphasis Panel (NSS)
Program Officer
Dicarlo-Cohen, Andrea L
Project Start
2008-07-03
Project End
2013-08-31
Budget Start
2012-09-01
Budget End
2013-08-31
Support Year
5
Fiscal Year
2012
Total Cost
$390,150
Indirect Cost
$155,436
Name
Brigham and Women's Hospital
Department
Type
DUNS #
030811269
City
Boston
State
MA
Country
United States
Zip Code
02115
Osuka, Akinori; Hanschen, Marc; Stoecklein, Veit et al. (2012) A protective role for inflammasome activation following injury. Shock 37:47-55