IL-12 protects bone marrow from and sensitizes intestinal tract to ionizing radiation
- Armed Forces Radiobiology Research Institute, Bethesda, MD (United States)
- Uniformed Services Univ. for Health Sciences, Bethesda, MD (United States)
- Genetics Institute, Cambridge, MA (United States)
IL-12, a potent stimulator of hemopoietic progenitor cells, was evaluated as a potential protector against {sup 60}Co-gamma radiation-induced lethal hemopoietic syndrome in mice. Administration of IL-12 before lethal irradiation of genetically distinct strains of mice, B6D2F{sub 1} and C3H/HeJ, protected a significant fraction of both strains of mice from death. Radioprotection was associated with a fivefold increase in the number of bone marrow cells at 6 days after irradiation. Even at supralethal doses of radiation (1200 cGy), the number of c-kit{sup +} bone marrow cells 3 days after irradiation was twofold greater in IL-12-treated mice than in saline-treated mice. However, mice that received IL-12 and 1200 cGy (B6D2F{sub 1}) or 900 cGy (C3H/HeJ) died of the gastrointestinal syndrome, as was evident by gross necroscopy and histologic evaluation, within 4 to 6 days after irradiation. Induction of the gastrointestinal syndrome in mice not treated with IL-12 required radiation doses of 1500 cGy or greater in both strains. Thus, at doses of radiation at which IL-12 still protects c-kit{sup +} hemopoietic cells, it sensitizes the intestinal tract to damage. Radioprotection with IL-12 was abrogated by anti-IL-1R or anti-stem cell factor Ab. Anti-IFN-{gamma} Ab did not affect IL-12-induced hemopoietic radioprotection, but abrogated sensitization of the intestinal tract by IL-12. The sensitizing effect of IL-12 may be related to its ability to prime mice to subsequent inflammatory challenge, as demonstrated by an almost 100-fold increase in circulating TNF and IL-6 levels in normal B6D2F{sub 1} mice challenged with IL-12 and LPS. This priming effect of IL-12 also was abrogated by anti-IFN-{gamma} Ab. 34 refs., 6 figs., 5 tabs.
- OSTI ID:
- 68474
- Journal Information:
- Journal of Immunology, Vol. 153, Issue 9; Other Information: PBD: 1 Nov 1994
- Country of Publication:
- United States
- Language:
- English
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