Interleukin-1 enhances survival of lethally irradiated mice treated with
allogeneic bone marrow cells
JJ Oppenheim, R Neta, P Tiberghien, R Gress, JJ Kenny and DL Longo
Division of Cancer Treatment, National Cancer Institute, Frederick, MD
21701-1013.
Interleukin-1 (IL-1) enhanced the capacity of allogeneic bone marrow (BM)
cells to promote survival of mice given doses of radiation (1,200 to 1,350
cGy) that are significantly higher than those generally used for BM
ablation (850 to 950 cGy). Three to five times greater numbers of lethally
irradiated (1,200 to 1,350 cGy) C57B1/6 (H-2b) mice given 10(7)
T-cell-depleted Balb/c (H-2d) BM cells survived over 6 weeks if also
treated with a single intraperitoneal (IP) dose of 10 micrograms IL-1 20
hours before or from 1 to 3 hours after radiation. The spleens of these
mice were reconstituted predominantly, but not exclusively, with donor
cells (54% to 91%). Histologic examination of the epidermal and
gastrointestinal tissues of mice surviving more than 6 weeks did not reveal
any evidence of graft-versus-host (GVH) disease; however, since 10% to 43%
of the mice died between days 30 and 46, the possibility of a GVH syndrome
in these mice cannot be excluded. The spleen cells from irradiated mice
given BM transplants and IL-1, which consisted of greater than or equal to
85% donor cells, were able to generate specific T-cell cytotoxic killing of
unrelated allogeneic donor cells but were unreactive to target cells
bearing either host or donor major histocompatibility complex (MHC) class I
antigens. Thus, long-term mixed chimeric survivors were tolerant to
recipient and donor alloantigens but exhibited immunologic competence.
These results show that IL-1 promotes survival of lethally irradiated mice
and that allogeneic hematopoietic cells in such animals develop tolerance
to host MHC antigens. Although there are many unanswered questions, these
data suggest that IL-1 may prove clinically useful in promoting BM
engraftment.
Volume 74,
Issue 6,
pp. 2257-2263,
11/01/1989
Copyright © 1989 by The American Society of Hematology
