The threat of nuclear disaster makes combined radiation and burn injury (CRI) a relevant topic when discussing modern trauma, as burn injuries are likely to occur with detonation of a conventional nuclear weapon. Previous studies in a murine model have shown that there is a breakdown of the gut epithelium and subsequent bacterial translocation into mesenteric lymph nodes after CRI. This study examines the early innate immune response of the small intestine after CRI. Using a previously established murine model of 5 to 5.5 Gy total body irradiation combined with 15% TBSA burn, the injury response of the small intestine was examined at 24, 48, and 72 hours by visual assessment, myeloperoxidase, and cytokine measurement. At 24 hours, intestinal damage as measured by villus blunting, crypt debris, and decreased mitosis, was apparent in all injury groups but the derangements persisted out to 72 hours only with CRI. The prolonged intestinal damage in CRI was accompanied by a 2-fold (P < .05) elevation in myeloperoxidase activity over sham animals at 48 hours and persisted as a 3-fold (P < .05) elevation at 72 hours after injury. Corresponding levels of KC were 8-fold (P < .05) higher than sham at 48hours with persistent elevation at 72 hours. An enhanced innate immune response, partially mediated by the influx of neutrophils into the gastrointestinal tract is contributing to the hyperinflammatory state seen after CRI. Attenuation of the local gastrointestinal inflammatory response may play a major role in managing victims after nuclear disaster.

Nuclear disaster associated with combined radiation injury (CRI) and trauma or burns results in higher mortality than component injuries. Early death is caused by sequelae of gastrointestinal (GI) leakiness such as bacterial translocation and shock. We developed a murine model to characterize GI injury after CRI and determine the extent of barrier disruption. Animals received radiation (5.5 Gy) alone or with 15% total body surface area (TBSA) scald burn and were euthanized at 24, 48, and 72 h. Mesenteric lymph node homogenate was plated on tryptic soy agar to assess for bacterial translocation. Tight junction protein, occludin, was characterized by Western blot and immunofluorescence. Intestinal histology was evaluated, and apoptosis was quantified using histone-associated DNA fragmentation enzyme-linked immunosorbent assay and Western blot for caspase-3 and caspase-8. At 72 h, a 100-fold increase in bacterial growth after CRI was observed. Occludin colocalization was reduced by radiation exposure, with largest differences in CRI at 24 and 48 h. Histopathology exhibited increased apoptosis in radiation alone and CRI animals at 24 and 48 h (P < 0.05). Further evidence of apoptotic activity in CRI was seen at 48 h, with 3-fold increases in enzyme-linked immunosorbent assay detection relative to all groups and caspase-8 activity relative to radiation alone and sham (P < 0.05). Prolonged epithelial apoptosis and disruption of tight junctions likely contribute to gut leakiness after CRI. Subsequent bacterial translocation to mesenteric lymph node potentially leads to sepsis and death and could serve as a target for mitigating agents to improve survival from CRI.

Carter, Stewart R. MD, BSc(Hons); Zahs, Anita BA; Palmer, Jessica L. MS; Brubaker, Aleah L. BSc(Hons); Wang, Lu MD; Ramirez, Luis BA; Choudhry, Mashkoor A. PhD; Yong, Sherri L. MD; Gamelli, Richard L. MD, FACS(Hon); Kovacs, Elizabeth J. PhD Author Information