Neutrophil Accumulation in the Small Intestine Contributes to Local Tissue Destruction Following Combined Radiation and Burn Injury

Abstract

Objective The threat of nuclear disaster makes combined radiation and thermal 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 following CRI. Methods Using a previously established murine model of 5 - 5.5Gy total body irradiation combined with 15% total body surface area burn, the injury response of the small intestine was examined at 24, 48 and 72hr by visual assessment, myeloperoxidase and cytokine measurement. Results At 24hr, intestinal damage as measured by villus blunting, crypt debris and decreased mitosis, was apparent in all injury groups but the derangements persisted out to 72hr only with CRI. The prolonged intestinal damage in CRI was accompanied by a 2-fold (p<0.05) elevation in myeloperoxidase activity over sham animals at 48hr and persisted as a 3-fold (p<0.05) elevation at 72hr post-injury. Corresponding levels of KC were 8-fold (p<0.05) higher than sham at 48hr with persistent elevation at 72hr. Conclusions An enhanced innate immune response, partially mediated by the influx of neutrophils into the gastrointestinal tract is contributing to the hyperinflammatory state seen following CRI. Attenuation of the local gastrointestinal inflammatory response may play a major role in managing victims following nuclear disaster.

Development of A Novel Murine Model of Combined Radiation and Peripheral Tissue Trauma Injuries

“…The extent of tissue damage caused by radiation has been reported previously (23, 24), but the effects of combined radiation and severe peripheral crush injury remain unclear. Histologic evaluation of the small intestine showed that initial damage to the gut at day 3 worsened at day 7 after TBX implantation (Fig.…”

“…In the model of combined burn (15% total-body surface) and TBI, combined injuries significantly increased lethality (9–11, 24). In an animal model of combined incisional wound inflicted 1 h prior to 9.6 Gy TBI, Kiang et al .…”

“…In the current animal model of combined injuries, we successfully evaluated functional and structural changes in gut and lungs. In the animal model of combined (TBI + burn) injuries, researchers reported increase in gut damage when compared to TBI or burn injuries alone (9–11, 24). They observed the characteristic shortening of villi in the small intestine, with an increase in apoptosis and loss of crypts that was exaggerated by combined injuries (24).…”

“…Tissues were embedded in paraffin, sectioned (5 μm) and stained with hematoxylin and eosin (H&E). Brightfield images of H&E-stained jejunal sections were acquired with a ZEN 2012 (Carl Zeiss Microscopy GmbH; Jena, Germany) and used to measure of villus height (according to a previously established method) measured starting at the crypt neck and ending at the villus tip (9). …”

“…In preclinical studies radiation has been combined with a number of different injuries (1, 4) including burns (9–11), sepsis (12), incisional wounds (13) and hemorrhage (14). These studies show the increased lethality in combined injuries, more severe tissue damage and the importance of timing of the wounding for survival.…”