Interleukin-1 administration before lethal irradiation and allogeneic bone marrow transplantation: early transient increase of peripheral granulocytes and successful engraftment with accelerated leukocyte, erythrocyte, and platelet recovery.
Administration of interleukin-1 beta (IL-1 beta) before a lethal irradiation with or without allogeneic bone marrow transplantation (BMT) protects greater than 90% of the irradiated mice. To approach the mechanisms responsible for the radioprotective effect of IL-1, we examined the effects of IL-1 pretreatment on engraftment and kinetics of peripheral blood, spleen, and marrow cell reconstitution after irradiation and BMT. Although the BMT was not necessary for the survival of the IL-1-pretreated lethally irradiated mice, allogeneic marrow did engraft in these mice as evaluated in the spleen and marrow 2 months after BMT. IL-1 pretreatment significantly accelerated hematopoietic recovery versus transplanted saline-treated controls with a pronounced enhancement of peripheral leukocyte, platelet, and erythrocyte recovery. Leukocyte recovery in IL-1-pretreated mice was unique in that IL-1 first induced an early transient (maximum at day 7) increase of peripheral granulocytes before accelerating leukocyte recovery after day 11. IL-1 pretreatment also significantly enhanced marrow cell recovery after allogeneic BMT with an eightfold increase in marrow cellularity from day 4 to 11 versus control transplanted mice. When lethal irradiation was not followed by allogeneic BMT. IL-1 pretreatment also affected the peripheral reconstitution of leukocytes, platelets, and erythrocytes. Interestingly, in the absence of BMT, IL-1 also induced an early circulation of peripheral granulocytes. Overall, our data demonstrate that a single administration of IL-1 before lethal irradiation and allogeneic BMT can induce an early transient increase of circulating granulocytes, followed by an accelerated multilineage recovery and long-term allogeneic engraftment.
Tiberghien
P
P
Unité de Greffe de Moelle Osseuse, Centre Regional de Transfusion Sanguine and Centre Hospitalier Universitaire, Besançon, France.
Laithier
V
V
Mabed
M
M
Racadot
E
E
Reynolds
C W
CW
Angonin
R
R
Loumi
R
R
Pavy
J J
JJ
Cahn
J Y
JY
Noir
A
A
D000818:Animals; D001853:Bone Marrow / Q000187:drug effects / Q000528:radiation effects; D016026:Bone Marrow Transplantation; D006098:Granulocytes / Q000187:drug effects* / Q000528:radiation effects; D006410:Hematopoiesis / Q000187:drug effects / Q000528:radiation effects; D007375:Interleukin-1 / Q000627:therapeutic use*; D007958:Leukocyte Count / Q000187:drug effects* / Q000528:radiation effects; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D010976:Platelet Count / Q000187:drug effects* / Q000528:radiation effects; D011828:Radiation Chimera; D013154:Spleen / Q000187:drug effects / Q000528:radiation effects; D014184:Transplantation, Homologous; D014916:Whole-Body Irradiation
D007375:Interleukin-1