Evidence that a transient enhancement of endogenous hematopoiesis contributes significantly to the favorable outcome following interleukin 1 pretreatment and allogeneic bone marrow transplantation.
The administration of IL-1, a potent radioprotective cytokine, before allogeneic BMT is associated with an early transient increase of circulating granulocytes, successful engraftment, and accelerated multilineage hematopoietic recovery. We have examined the effects of IL-1 alpha pretreatment on the engraftment of an allogeneic BMT unable to sustain survival by itself after a lethal irradiation: (1) transplantation of a limited amount of marrow cells and (2) transplantation several days after irradiation. IL-1 was unable to allow the engraftment of an early quantitatively inadequate BMT. However, delayed BMT with limited amounts of marrow cells was associated with engraftment in IL-1 pretreated recipients. Engraftment of a late (day 12) BMT in these IL-1-pretreated mice was comparable to the engraftment of a similar day 12 allogeneic BMT in non-IL-1-pretreated mice rescued from the lethal irradiation by an early (day 1) syngeneic graft. These findings demonstrate that IL-1 pretreatment can result in a dissociation between BMT-induced survival and engraftment and suggest that the favorable effects of IL-1 pretreatment in an allogeneic BMT setting are mainly mediated through a transient enhancement of endogenous hematopoiesis and not through a direct effect on the allogeneic stem cells present in the marrow graft.
Herve
V
V
Histocompatibility and Immuno-Molecular Therapeutics Laboratory, E.T.S. Franche-Comte, France.
Mabed
M
M
Laithier
V
V
Pavy
J J
JJ
Angonin
R
R
Contassot
E
E
Certoux
J M
JM
Cahn
J Y
JY
Herve
P
P
Tiberghien
P
P
D000818:Animals; D016026:Bone Marrow Transplantation / Q000276:immunology*; D006085:Graft Survival / Q000187:drug effects; D006410:Hematopoiesis / Q000187:drug effects*; D007375:Interleukin-1 / Q000494:pharmacology*; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D011837:Radiation-Protective Agents / Q000494:pharmacology*; D014916:Whole-Body Irradiation
D007375:Interleukin-1; D011837:Radiation-Protective Agents