Countermeasures against radiation effects on the gastrointestinal tract due to a nuclear injury are essential to improve survival in case of such an injury. Large doses of total body radiation lead to immediate death due to neurological obliteration. At lesser doses, gastrointestinal syndrome predominates and is characterized by nausea, vomiting, and diarrhea. As the intestinal mucosa breaks down from the radiation, bacteria can be transported into the blood stream, leading to overwhelming sepsis. It is critical that interventions be developed that can help the victims of gastrointestinal radiation toxicity because this would lead to significant improvements in survival from an injury. These interventions would benefit the population exposed to a radiation disaster and the first-responders who enter the radiation area for medical, military, and clean-up purposes. Ideally, such interventions should be easy to administer, have minimal toxicity, be capable of being stockpiled for rapid local distribution, and be effective in preventing the adverse effects on the intestinal tract from radiation. Interleukin-11 is a pleiotrophic cytokine that has anti-inflammatory properties. Clinically, this drug has been developed to improve platelet counts diminished by chemotherapy. It is typically given as a subcutaneous injection that has significant side effects, mostly due to excess fluid retention. We have shown that there is significant reduction in the effects of radiation on the intestine when IL-11 is delivered locally to the intestinal lumen. This method of delivery lacks systemic absorption of the drug and, therefore, lacks systemic toxicity. We propose to utilize a microencapsulated form of IL-11 as an oral preparation to prevent radiation damage to the intestinal tract in mice. These studies will examine the effect of this compound when given orally prior to radiation and when given after radiation exposure. This will demonstrate the prophylactic and mitigating properties of this compound against radiation enteritis. Measured outcomes will include alterations in lethality from radiation and alterations in intestinal pathology in treated versus untreated animals. From a public health perspective, development of this compound could result in a pill that could be taken in the event of a nuclear bomb to prevent death from intestinal damage from radiation. The pill would have minimal or no side effects and could be available to be taken immediately at the first warning or after announcement of a nuclear explosion.
| Burnett, Alexander F; Biju, Prabath G; Lui, Huanli et al. (2013) Oral interleukin 11 as a countermeasure to lethal total-body irradiation in a murine model. Radiat Res 180:595-602 |
