The role of recombinant cytokines and other immunomodulators on engraftment following allogeneic bone marrow transplantation in mice.
BALB/c mice were conditioned by total body irradiation (TBI) with a suboptimal (475 cGy) or optimal (600 cGy) radiation dose for induction of chimerism subsequent to administration of 10(7) (BALB/c x C57BL/6) F1 (F1) bone marrow cells in order to test whether a variety of recombinant cytokines and other immunomodulators caused positive or negative effects on engraftment at different time intervals post-bone marrow transplantation (BMT). Engraftment in recipient mice conditioned by the minimal dose of TBI permitting 100% induction of chimerism (600 cGy) was not impaired following treatment with recombinant human interleukin 2 (IL2) (10(4) Cetus Units x 3/day i.p.), alpha interferon (alpha IFN) (10(4) units/day i.p.), gamma interferon (gamma IFN) (10(4) U/day i.p.) and combinations of IL2 + alpha IFN as well as IL2 + gamma IFN given either 5 days prior to or 5 days following BMT. Likewise, neither PGE2 (50 micrograms x 2/day i.p.) nor indomethacin (25 micrograms x 2/day i.p.) given either immediately prior to or immediately following BMT for 3 consecutive days had any detectable effect on chimerism. To investigate the putative beneficial effects of IL2 in enhancing marrow engraftment, BALB/c mice were irradiated with a suboptimal dose of TBI (475 cGy) followed by reconstitution with 10(7) F1 marrow cells supplemented with 2 x 10(6) F1 spleen cells. IL2 (10(4) U x 3/day i.p. x 5 days) was administered either prior to TBI, between TBI and BMT, immediately following BMT, or starting 2 weeks post-BMT.(ABSTRACT TRUNCATED AT 250 WORDS)
Bieder
A
A
Department of Bone Marrow Transplantation, Hadassah University Hospital, Jerusalem, Israel.
Weiss
L
L
Slavin
S
S
D000818:Animals; D016026:Bone Marrow Transplantation; D002678:Chimera; D016207:Cytokines / Q000627:therapeutic use*; D004195:Disease Models, Animal; D006084:Graft Rejection; D006085:Graft Survival; D007376:Interleukin-2 / Q000627:therapeutic use; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D014184:Transplantation, Homologous; D014916:Whole-Body Irradiation
D016207:Cytokines; D007376:Interleukin-2