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 BRIT is associated with an early transient increase of circ ulating granulocytes, successful engraftment, and accelerated multilin eage hematopoietic recovery. We have examined the effects of IL-1 alph a pretreatment on the engraftment of an allogeneic BRIT unable to sust ain survival by itself after a lethal irradiation: (1) transplantation of a limited amount of marrow cells and (2) transplantation several d ays after irradiation. IL-1 was unable to allow the engraftment of an early quantitatively inadequate BRIT. However, delayed BRIT with limit ed amounts of marrow cells was associated with engraftment in IL-1-pre treated recipients. Engraftment of a late (day 12) BRIT in these IL-1- pretreated mice was comparable to the engraftment of a similar day 12 allogeneic BRIT in non-IL-1-pretreated mice rescued from the lethal ir radiation by an early (day 1) syngeneic graft. These findings demonstr ate that IL-1 pretreatment can result in a dissociation between BMT-in duced survival and engraftment and suggest that the favorable effects of IL-1 pretreatment in an allogeneic BRIT setting are mainly mediated through a transient enhancement of endogenous hematopoiesis and not t hrough a direct effect on the allogeneic stem cells present in the mar row graft.