title: Interleukin 1 beta initially sensitizes and subsequently protects murine intestinal stem cells exposed to photon radiation.
abstract: 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-1 beta (4 micrograms/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 micrograms/kg. However, doses ranging from 10 to 100 micrograms/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.
authors.affiliation: Department of Radiation Oncology, Stanford University School of Medicine, California 94305.
authors.forename: S L
authors.initials: SL
authors.lastname: Hancock
authors.forename: R T
authors.initials: RT
authors.lastname: Chung
authors.forename: R S
authors.initials: RS
authors.lastname: Cox
authors.forename: R F
authors.initials: RF
authors.lastname: Kallman
mesh_terms: D000818:Animals; D002470:Cell Survival / Q000187:drug effects; D004307:Dose-Response Relationship, Radiation; D004334:Drug Administration Schedule; D007375:Interleukin-1 / Q000008:administration & dosage / Q000494:pharmacology*; D007413:Intestinal Mucosa / Q000187:drug effects / Q000528:radiation effects*; D007421:Intestine, Small / Q000528:radiation effects*; D008297:Male; D051379:Mice; D011836:Radiation Tolerance / Q000187:drug effects; D011837:Radiation-Protective Agents / Q000008:administration & dosage / Q000494:pharmacology; D013234:Stem Cells / Q000187:drug effects / Q000528:radiation effects*
chemical_list: D007375:Interleukin-1; D011837:Radiation-Protective Agents