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Utility of interleukin-1 in therapy of radiation injury as studied in small and large animal models

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Biotherapy

Summary and conclusions

Our results demonstrate that IL-1 promotes hematopoiesis in normal and radiation compromised animals. IL-1 protected mice from lethal hematopoietic syndrome when given before irradiation. Given after irradiation, IL-1 promoted recovery of mice and primates from radiation injury.

A comparison of the effects of IL-1 in three different species indicated that hematopoiesis of mice, monkeys,and dogs is upregulated in a similar fashion by IL-1. These three species, however, vary greatly in their sensitivity to IL-1. Whereas mice and dogs tolerated doses greater than 1000 ⧎g/Kg of IL-1, 10 ⧎g/Kg of IL-1 in rhesus monkeys resulted in considerable toxic effects.

Several activities of IL-1 may explain its bone marrow restorative properties. The induction with IL-1 of several hematopoietic growth factors: GM-CSF, G-CSF, M-CSF, IL 3, and IL 6, clearly contributes to the accelerated growth and differentiation of hematopoietic progenitor cells. The induction of scavenger proteins may serve to reduce post irradiation oxidative damage.

Our work raised a number of additional questions concerning the potential therapeutic utility of IL-1. The ability of IL-1 to promote engraftment of allogeneic bone marrow cells will require further study. The optimal dosage, schedule, and route for IL-1 induction of hematopoiesis will need to be established. The observed synergy of IL-1 with TNF, IL 6, or CSF's may be useful in reducing the requisite doses of cytokines from pharmacological to physiological levels with concomitant reduction in toxic effects. The choice of proper cytokine combinations, however, may also be dependent on the clinical status of the patients.

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  1. Armed Forces Radiobiology Research Institute and Naval Medical Research Institute, 20814, Bethesda, MD, USA

    R. Neta, R. Monroy & T. J. MacVittie

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  1. R. Neta
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Neta, R., Monroy, R. & MacVittie, T.J. Utility of interleukin-1 in therapy of radiation injury as studied in small and large animal models. Biotherapy 1, 301–311 (1989). https://doi.org/10.1007/BF02171006

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