UNIVERSITY OF ARKANSAS SYSTEM
The development of non-toxic medical countermeasures against gastrointestinal radiation injury is an
unmet need. These countermeasures would benefit the population exposed to a radiation disaster or nuclear
attack, as well as first-responders who enter a contaminated area for medical, military, or clean-up purposes.
Ideally, such interventions should be easy to administer, have minimal toxicity, be capable of being
stockpiled for rapid distribution, and be effective in preventing the adverse effects of radiation on the
intestinal tract. Agents that can protect the gut when given after radiation exposure (mitigating agents) are
the top priority.
lnterleukin-11 (IL-11) is a pleiotrophic cytokine that has anti-inflammatory properties. Clinically, this cytokine
was developed as a drug to improve platelet counts diminished by chemotherapy. When given
subcutaneously, however, IL-11 has significant side effects, such as, fluid retention, particularly in the lungs.
Experiments in dogs have shown that when IL-11 is given systemically with a modest dose of total body
radiation (2 Gy), a higher percentage of animals died from pneumonitis when compared with animals
irradiated without IL-11. On the other hand, IL-11 administered orally to animals and humans is not
absorbed systemically and is free of systemic side effects.
We have previously shown in a rat model that local administration of IL-11 in liquid form to the gut
significantly reduced radiation enteropathy. The intestinal lining exposed to IL-11 had greater mucosal
surface area with less ulceration, improved crypt colony formation, and less inflammatory response than
irradiated gut not exposed to IL-11. This early data led to our present study of orally administered
interleukin-11 as a countermeasure against intestinal damage from total body radiation.