IL-12 facilitates both the recovery of endogenous hematopoiesis and the engraftment of stem cells after ionizing radiation

Experimental Hematology
Tingchao ChenYi Zhao

Abstract

Severe myelosuppression is a common side effect of radiotherapy or chemotherapy. Methods have been developed to protect patients by stimulating white blood cell or red blood cell recovery/production using growth factors such as G-CSF or EPO. However, there is no available means to stimulate the full-lineage blood cell recovery from severe myelosuppression. In this study, we used lethally or sublethally irradiated animal models to evaluate the hematopoiesis stimulating effect of IL-12. IL-12-treated lethally or sublethally irradiated animals were examined for the survival/lifespan, the function assays (bone marrow transplantation, CFU-S(12), CFC) of bone marrow cell subsets, and apoptosis assay. Using a low dose of IL-12 (10 times lower than previously reported dose), 91.4% of lethally irradiated animals survived long term without adverse effects on the gastrointestinal (GI) system. The reconstituted hematopoietic system was derived from long-term reconstituting hematopoietic stem cells (LTR HSC), which reconstituted hematopoiesis both endogenously after lethal radiation and in secondary recipients by bone marrow transplantation (BMT). IL-12 significantly attenuated the decline of blood cell counts in sublethally irradiated anim...Continue Reading

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