Objective: The immune system is highly sensitive to ionizing radiation and, therefore, death from secondary infections due to decreased leukocyte counts is a major threat following nuclear accidents or attacks. To protect individuals with depressed immune systems, strategies must be developed that can easily, safely, and rapidly restore the ability to fight common infections after radiation exposure. We tested whether elevation of body temperature to the fever-range could improve the reconstitution and/or function of peripheral blood leukocytes after radiation exposure.

Methods: C57BL/6 mice were given a non-myeloablative dose (3Gy) of total body irradiation (TBI) followed 2 hours later by a 6 hour whole body hyperthermia (WBH) treatment (core temperature was maintained at 39.5°C). Blood was collected one week prior to, immediately following, and at weekly intervals after TBI. Total blood leukocyteswere stained for B cells (B220+), T cells (CD3+), NK cells (NK1.1), and granulocytes (GR-1) and analyzed by flow cytometry. Percent cell population recovery was then calculated. Serum concentrations of G-CSF, GM-CSF, and MIP-2 were measured by ELISA.

Results: In mice treated with WBH following TBI, a significant increase in recovery of peripheral blood granulocytes was observed by day 8 compared to mice that received radiation alone. WBH alone did not result in a significant change in blood leukocyte numbers. Furthermore, results from these preliminary experiments indicate that G-CSF concentrations are increased two fold in the serum of radiated/heated mice correlating with the increased granulocyte recovery.

Conclusions: Granulocytes are a front line defense against bacterial infection; therefore the ability to speed the rate of recovery of these cells, using mild hyperthermia, could lead to an important new therapeutic intervention for the protection against secondary infections following ionizing radiation exposure. These data reveal a previously unexplored role of body temperature in regulation of marrow output following stress. Current work is exploring the contribution of thermally regulated, marrow stimulating cytokines toward immune cell reconstitution in peripheral blood after radiation.
* These authors contributed equally to this work.