CpG ODN treatment in radiation-combined injury (172.31)

Abstract

Abstract In the scenario of a nuclear event, radiation injury will be accompanied by additional trauma, especially burns. We developed a mouse model to allow us to study the changes in the immune system induced by these injuries. In this study, we tested the potential of using CpG oligodeoxynucleotides (ODN) as treatments in radiation combined injury (RCI). Mice were exposed to 1, 4 and 6 Gy whole body radiation and underwent near simultaneous burn injury. One day after injury, mice were injected with either CpG ODNs or saline. Seven days later, sepsis was induced by cecal ligation and puncture (CLP) and survival was recorded. Spleen immune cell subsets were assessed by FACS and inflammatory cytokine production by splenocytes was determined at 7 days after CLP. To investigate the role of regulatory T cells (Tregs) in this model, mice were Treg depleted after class A CpG treatment. Treatment with class A CpG increased survival after RCI with 1 Gy followed by CLP significantly whereas treatment with class B or C did not. Class A treatment also conferred a survival benefit following RCI with 4 and 6 Gy. Inflammatory cytokine production was decreased with class A treatment but not with class B or C. The effects of class A treatment were not seen in Treg depleted mice. Class A CpG tracking showed increased uptake in Tregs when compared to class B or C. In summary, CpG treatment is effective in enhancing host defense mechanisms following RCI.