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Interleukin 1ß Initially Sensitizes and Subsequently Protects Murine Intestinal Stem Cells Exposed to Photon Radiation¹

Department of Radiation Oncology, Divisions of Radiation Therapy and Radiobiology, Stanford University School of Medicine, Stanford, California 94305

Interleukin 1 (IL-1) has been shown to prevent early bone marrow-related death following total-body irradiation, by protecting hematopoietic stem cells and speeding marrow repopulation. This study assesses the effect of IL-1 on the radiation response of the intestinal mucosal stem cell, a nonhematopoietic normal cell relevant to clinical radiation therapy. As observed with bone marrow, administration of human recombinant IL-1ß (4 µg/kg) to C3H/Km mice 20 h prior to total-body irradiation modestly protected duodenal crypt cells. In contrast to bone marrow, IL-1 given 4 or 8 h before radiation sensitized intestinal crypt cells. IL-1 exposure did not substantially alter the slope of the crypt cell survival curve but did affect the shoulder: the X-ray survival curve was offset to the right by 1.01 ± 0.06 Gy when IL-1 was given 20 h earlier and by 1.28 ± 0.08 Gy to the left at the 4-h interval. Protection was greatest when IL-1 was administered 20 h before irradiation, but minimal effects persisted as long as 7 days after a single injection. The magnitude of radioprotection at 20 h or of radiosensitization at 4 h increased rapidly as IL-1 dose increased from 0 to 4 µg/kg. However, doses ranging from 10 to 100 µg/kg produced no further difference in radiation response. Animals treated with saline or IL-1 had similar core temperatures from 4 to 24 h after administration, suggesting that thermal changes were not responsible for either sensitization or protection. Mice irradiated 20 h after IL-1 had significantly greater crypt cell survival than saline-treated irradiated controls at all assay times, which ranged from 54 to 126 h following irradiation. The intervals to maximum crypt depopulation and initiation of repopulation were identical in both saline- and IL-1-treated groups, suggesting that IL-1 altered absolute stem cell survival but not the kinetics of repopulation.

¹ This work was supported by Institutional Seed Grants from the American Cancer Society (IN-32-Z) and the NIH B.R.S.G (NIH RR5353-29).

² To whom requests for reprints should be addressed, at Department of Radiation Oncology, Stanford University Medical Center, A089, Stanford, CA 94305.

Received 7/12/90. Accepted 2/19/91.

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