Jd. Lutton et al., SYNERGISTIC EFFECT OF HEME AND IL-1 ON HEMATOPOIETIC STROMAL REGENERATION AFTER RADIATION, American journal of hematology, 44(3), 1993, pp. 172-178
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.