SYNERGISTIC EFFECT OF HEME AND IL-1 ON HEMATOPOIETIC STROMAL REGENERATION AFTER RADIATION

Results from this study show that a combination of heme and interleuki n-1 (IL-1) treatment resulted in the most improved recovery of hematop oietic-stromal regeneration after sublethal irradiation. Less pronounc ed effects were obtained when heme or IL-1 were given singly. Subletha l irradiation of mice produced an initial (as early as day 1) intense depression of the hematopoietic system as evidenced by leukopenia. In vivo treatment of animals with heme in combination with IL-1, accelera ted hematopoietic and stromal regeneration as determined by hematopoie tic spleen colony forming unit assay (CFU-S), erythroid (BFU-E), myelo id (CFU-GM) clonal cultures, long-term bone marrow cultures (LTBMC), a nd the ability to regenerate hematopoiesis by ectopic (renal) stromal hemopoietic transplantation. Sixteen days after irradiation, leukocyte levels in heme and IL-1 treatment groups were higher than non-treated animals and were near normal values by 27 days. One day after irradia tion, the capacity of stromal progenitors to form new bone and hematop oietic cells (ectopic foci) was severely impaired, but recovered after 2-4 weeks. This recovery process was accelerated in heme and IL-1-tre ated animals. BFU-E, CFU-GM, and CFU-S capacity was also severely impa ired in all animals 1-27 days after irradiation. CFU-S was only 0.15% of control by day 1 and 5% of control by day 16. Treatment with heme o r IL-1 improved recovery by as much as 70% after 27 days of irradiatio n. A similar but enhanced recovery was seen for BFU-E and CFU-GM, with erythroid recovery the best. Total cellularity, adherent cell layer ( ACL) formation, and clonogenic capacity by LTBMCs (10 weeks) derived f rom irradiated animals was severely reduced, whereas the hematopoietic capacity by LTBMCs derived from heme- and IL-1-treated animals had re covery values similar to non-irradiated controls. These results sugges t therapeutic use of heme and IL-1 after chemotherapy or bone marrow d epression may be beneficial. (C) 1993 Wiley-Liss, Inc.