In lethally irradiated mice interleukin-12 protects bone marrow but sensitizes intestinal tract to damage from ionizing radiation.
Administration of IL-12 prior to lethal irradiation, protected a significant fraction of mice from 60Co-gamma radiation-induced lethal hematopoietic syndrome. Radioprotection was associated with an increase in the number of c-kit+ bone marrow cells (BMC) in IL-12 treated mice compared to saline-treated mice. Even after supralethal doses of radiation (1200 cGy), IL-12-treated mice had twofold greater numbers of c-kit+ BMC than controls. However the mice receiving IL-12 and 1200 cGy died of the gastrointestinal (GI) syndrome, evident by gross necroscopy and histological evaluation, within 4 to 6 days after irradiation. Induction of the GI syndrome in mice not treated with IL-12 required radiation doses of 1600 cGy. Thus, at doses of radiation at which IL-12 still protects c-kit+ hematopoietic cells, it sensitizes the intestinal tract to damage. Radioprotection with IL-12 was abrogated by anti-IL-1R or anti-SCF antibody, but not anti-IFN gamma antibody. In contrast, anti-IFN gamma antibody abrogated sensitization of the intestinal tract by IL-12.
Neta
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Department of Experimental Hematology, Armed Forces Radiobiology Research Institute, Bethesda, Maryland 20889-5603, USA.
Stiefel
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SM
Ali
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N
D000818:Animals; D001853:Bone Marrow / Q000187:drug effects / Q000528:radiation effects; D005720:Gamma Rays; D006410:Hematopoiesis / Q000528:radiation effects*; D016298:Hematopoietic Cell Growth Factors / Q000502:physiology; D007371:Interferon-gamma / Q000502:physiology; D007422:Intestines / Q000528:radiation effects*; D051379:Mice; D011837:Radiation-Protective Agents; D011838:Radiation-Sensitizing Agents; D017472:Receptors, Interleukin-1 / Q000502:physiology; D019089:Stem Cell Factor
D016298:Hematopoietic Cell Growth Factors; D011837:Radiation-Protective Agents; D011838:Radiation-Sensitizing Agents; D017472:Receptors, Interleukin-1; D019089:Stem Cell Factor; D007371:Interferon-gamma