Radioprotection and therapy of radiation injury with cytokines.

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 therapeutically after irradiation, IL 1 promoted recovery from radiation injury. 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 reduce oxidative damage after irradiation. Our work raises 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, thus reducing toxic effects. The observation that the cyclooxygenase inhibitor, indomethacin, does not inhibit IL 1 radioprotection may allow us to combat some of the toxic manifestations of IL 1 and to preserve its beneficial actions. Clinical trials with IL 1 in patients, now in progress, should establish whether this cytokine may be useful in reversing the myelotoxic effects of radiotherapy and chemotherapy in humans.