VCURES researchers target the immune system to improve survival of victims who have suffered severe traumatic shock

By Sathya Achia Abraham

Virginia Commonwealth University researchers hope to improve the survival of severely injured soldiers and civilians with the discovery that a naturally occurring hormonal agent known as androstenetriol has a very powerful effect on the immune system.

Just minutes after a traumatic episode resulting in injured tissue and massive bleeding, the immune system responds by entering a state of uncontrolled inflammation that wreaks havoc on the body. The inflammation can damage multiple organs causing them to fail, eventually taking the life of the injured.

Roger Loria, Ph.D., a professor of microbiology, immunology, pathology and emergency medicine at the School of Medicine, together with colleagues in the VCU Reanimation Engineering Shock Center, report that androstenetriol enhances the body’s existing immune capabilities and enables the body to resist lethal insults such as infections, radiation poisoning, and now, traumatic hemorrhagic shock.

“Immune disruption is a major component of the shock response in trauma and hemorrhage. Restoring the balance of the immune response early after injury greatly reduces the damage and injury caused by shock trauma and hemorrhage and leads to improved survival,” Loria said.

“Our findings show that androstenetriol has the potential to be used to provide an immune shield after trauma and blood loss following accidents, surgery, and battle field injury,” he said.

Loria and his colleagues showed for the first time that a single injection of androstenetriol was associated with a significant increase in survival even after major blood loss up to about 55 percent to 60 percent in a rat model. The study was published in the September issue of the Journal TRAUMA® Injury, Infection, and Critical Care

Furthermore androstenetriol’s properties may provide significant protection from secondary infections following severe traumatic shock.

“This is a very simple and cost-effective intervention which could be carried out by field paramedics or combat medics. By naturally enhancing the body’s immune system, it is likely that patients would recover much faster and be a less risk for lethal complications,” Loria said.

For more than 25 years, Loria has investigated immunological changes following traumatic/hemorrhagic shock, including interventions with androstene derivatives. The research focuses on the pathogenic and immunological responses following virus infections, particularly human enteric viruses. His other work centers on immune up-regulation following infections, cancer and radiation.

The next step for Loria and the VCURES team will be to extend this work to human clinical trials to determine if androstenetriol is safe and effective for use in humans.

This work was supported by a grant from the Office of Naval Research.

Along with Loria, VCURES researchers, Andreea C. Marcu, M.D., Kristin E. Paccione, R. Wayne Barbee, Ph.D., Robert F. Diegelmann, Ph.D., Rao R. Ivatury, M.D., Kevin R. Ward, M.D., contributed to this work.