Insulin-like growth factor-I enhances lymphoid and myeloid reconstitution after allogeneic bone marrow transplantation.

被引:54
作者
Alpdogan, Ö
Muriglan, SJ
Kappel, BJ
Doubrovina, E
Schmaltz, C
Schiro, R
Eng, JM
Greenberg, AS
Willis, LM
Rotolo, JA
O'Reilly, RJ
van den Brink, MRM
机构
[1] Mem Sloan Kettering Canc Ctr, Dept Med, New York, NY 10021 USA
[2] Mem Sloan Kettering Canc Ctr, Dept Pediat, New York, NY 10021 USA
关键词
D O I
10.1097/01.TP.0000070167.81584.A2
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
Background. Prolonged immunodeficiency after allogeneic bone marrow transplantation (allo BMT) results in significant morbidity and mortality from infection. Previous studies in murine syngeneic BAIT 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. Conclusion. IGF-I administration can enhance lymphoid and myeloid reconstitution after allo BMT without aggravating GVHD.
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页码:1977 / 1983
页数:7
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