title: Insulin-like growth factor-I enhances lymphoid and myeloid reconstitution after allogeneic bone marrow transplantation.
abstract: 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.
authors.affiliation: 3 Department of Medicine, Memorial Sloan-Kettering Cancer Center, New York, NY.
authors.forename: Onder
authors.initials: O
authors.lastname: Alpdogan
authors.forename: Stephanie J
authors.initials: SJ
authors.lastname: Muriglan
authors.forename: Barry J
authors.initials: BJ
authors.lastname: Kappel
authors.forename: Ekaterina
authors.initials: E
authors.lastname: Doubrovina
authors.forename: Cornelius
authors.initials: C
authors.lastname: Schmaltz
authors.forename: Raffaella
authors.initials: R
authors.lastname: Schiro
authors.forename: Jeffrey M
authors.initials: JM
authors.lastname: Eng
authors.forename: Andrew S
authors.initials: AS
authors.lastname: Greenberg
authors.forename: Lucy M
authors.initials: LM
authors.lastname: Willis
authors.forename: Jimmy A
authors.initials: JA
authors.lastname: Rotolo
authors.forename: Richard J
authors.initials: RJ
authors.lastname: O'Reilly
authors.forename: Marcel R M
authors.initials: MR
authors.lastname: van den Brink
mesh_terms: 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
chemical_list: D007334:Insulin-Like Growth Factor I