When a person is exposed to high levels of radiation, however, the ability to generate neutrophils is almost obliterated. "It's a perfect storm of disease-causing events," Guinan remarks. "Radiation results in bacteria and endotoxins entering the bloodstream at the same time that the body's defenses are lowered."
The treatment approach developed by Guinan, Levy and their colleagues takes direct aim at two potential contributors to radiation sickness: bacteria and the endotoxins on their surface. "We theorized that a two-drug therapy would be most effective," Levy states. "Others had already shown some benefit to treatment with fluoroquinolones after radiation; at least part of the benefit came from killing bacteria in the blood. The second, rBPI21, would bind to, neutralize, and 'mop up' the endotoxins released by the dying bacteria, thereby removing the trigger of the inflammation process."
In the study, researchers exposed mice to radiation levels of 7 gray (by comparison, the amount emitted by a standard X-ray machine is 0.01 grays.) At those levels, radiation is 95 percent lethal to mice within 30 days.
Twenty-four hours after the radiation exposure, researchers began treating some of the mice with daily doses of fluoroquinolone antibiotic, some with twice-daily doses of rBPI21, and some with both. The mice that received both agents not only had much higher survival rates than the others, but their ability to generate new blood cells also recovered much more quickly.
The promise of this approach is underscored by the nature of the two agents, the study authors say. Both have a
|Contact: Teresa Herbert|
Dana-Farber Cancer Institute