Insulin-like growth factor-I enhances lymphoid and myeloid reconstitution after allogeneic bone marrow transplantation.
BACKGROUND
Prolonged immunodeficiency after allogeneic bone marrow transplantation (allo BMT) results in significant morbidity and mortality from infection. Previous studies in murine syngeneic BMT models have demonstrated that posttransplantation insulin-like growth factor (IGF)-I administration could enhance immune reconstitution.


METHODS
To analyze the effects of IGF-I on immune reconstitution and graft-versus-host disease (GVHD) after allo BMT, we used murine models for MHC-matched and -mismatched allo BMT. Young (3-month-old) recipient mice received 4 mg/kg per day of human IGF-I from days 14 to 28 by continuous subcutaneous administration.


RESULTS
IGF-I administration resulted in increased thymic precursor populations (triple negative-2 and triple negative-3) as determined on day 28 but had no effect on overall thymic cellularity. In the periphery, the numbers of donor-derived splenic CD3+ T cells were increased and these cells had an improved proliferative response to mitogen stimulation. IGF-I treatment also significantly increased the numbers of pro-, pre-, and mature B cells and myeloid cell populations in the spleens of allo BMT recipients on day 28. The administration of IGF-I in combination with interleukin 7 had a remarkable additive effect on B-cell, but not on T-cell, lymphopoiesis. Finally, we tested the effects of IGF-I administration on the development of GVHD in three different MHC-matched and -mismatched models and found no changes in GVHD morbidity and mortality.


CONCLUSIONS
IGF-I administration can enhance lymphoid and myeloid reconstitution after allo BMT without aggravating GVHD.
Alpdogan
Onder
O
3 Department of Medicine, Memorial Sloan-Kettering Cancer Center, New York, NY.
Muriglan
Stephanie J
SJ
Kappel
Barry J
BJ
Doubrovina
Ekaterina
E
Schmaltz
Cornelius
C
Schiro
Raffaella
R
Eng
Jeffrey M
JM
Greenberg
Andrew S
AS
Willis
Lucy M
LM
Rotolo
Jimmy A
JA
O'Reilly
Richard J
RJ
van den Brink
Marcel R M
MR
D000818:Animals; D001854:Bone Marrow Cells / Q000166:cytology / Q000187:drug effects; D016026:Bone Marrow Transplantation / Q000276:immunology / Q000502:physiology*; D002454:Cell Differentiation / Q000187:drug effects; D006086:Graft vs Host Disease / Q000517:prevention & control*; D006098:Granulocytes / Q000187:drug effects / Q000502:physiology; D006801:Humans; D007263:Infusions, Parenteral; D007334:Insulin-Like Growth Factor I / Q000008:administration & dosage / Q000627:therapeutic use*; D008213:Lymphocyte Activation / Q000187:drug effects; D008285:Major Histocompatibility Complex; D051379:Mice; D008809:Mice, Inbred C3H; D008810:Mice, Inbred C57BL; D008815:Mice, Inbred Strains; D013601:T-Lymphocytes / Q000187:drug effects / Q000276:immunology*; D014184:Transplantation, Homologous; D014185:Transplantation, Isogeneic
D007334:Insulin-Like Growth Factor I