Research ArticleRadiation Toxicity

Bactericidal/Permeability-Increasing Protein (rBPI21) and Fluoroquinolone Mitigate Radiation-Induced Bone Marrow Aplasia and Death

Science Translational Medicine  23 Nov 2011:
Vol. 3, Issue 110, pp. 110ra118
DOI: 10.1126/scitranslmed.3003126

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Reducing Risks of Radiation

Radiation—intentional or not—kills dividing cells, dealing a double whammy to the body. The demise of dividing intestinal cells renders the gut leaky, letting microbes in and shuttling down the immune cell production line in the bone marrow, leaving the body extra susceptible to the invading microbes. In a new approach to treating these lethal effects of radiation, Guinan et al. deliver a double whammy of their own by combining an antibiotic and an inhibitor of dangerous microbial endotoxin to prevent death by radiation in mice. The dual drugs are effective when given 24 hours after the radiation, a boon for use in a disaster where immediate treatment might not be possible.

The authors found a clue for this new approach to radiation mitigation by studying patients irradiated in preparation for a bone marrow transplant. Among the responses was a drop in serum concentrations of BPI (bactericidal/permeability-increasing protein), a protective protein that binds to lipopolysaccharide, which is shed by microbes and can cause severe lethal reactions in patients. They reasoned that replacing the declining BPI could be beneficial and tested this idea in mice. Although BPI alone did not help irradiated mice survive, when BPI was given together with an antibiotic, about 70 to 80% of the animals lived, whereas almost none of the untreated animals were alive after 20 days. The combined BPI/antibiotic therapy also caused a rebound in the number of cells in the bone marrow after their radiation-induced depletion.

What makes this combo treatment particularly appealing is the fact that both BPI and the antibiotic have previously been used safely in humans, an important point when calculating the risk-benefit ratio of treating individuals whose exact dose of radiation may not be clear. With nontoxic agents, one can more comfortably treat someone who may have received a small dose. This advantage, plus the fact that, at least in mice, the BPI/antibiotic can be administered a full day after exposure and still be effective, suggests that this double-drug approach should be tested for use in humans.

Footnotes

  • Present address: Infinity Pharmaceuticals, 780 Memorial Drive, Cambridge, MA 02139, USA.

  • Present address: Weizmann Institute, Rehovot 76100, Israel.

  • § Present address: Feinberg School of Medicine, Northwestern University, 420 East Superior Street, Chicago, IL 60611, USA.

  • || Present address: Georgia Institute of Technology; Atlanta, GA 30332, USA.