Human insulin-like growth factor I exerts hematopoietic growth-promoting effects after in vivo administration.
Recombinant human insulin-like growth factor I (rhIGF-I) was administered to mice to determine its effect on hematopoiesis. Mice given intraperitoneal (IP) injections of 5 micrograms rhIGF-I for 7 days exhibited a significant increase in bone marrow (BM) hematopoietic progenitor cells, suggesting that rhIGF-I acts as a hematopoietic growth factor. Treatment with rhIGF-I also resulted in increases in erythroid precursor cells. Mice were then placed on azidothymidine (AZT), which produces significant myelotoxic effects. Splenic and BM progenitor cell content and hematocrit values were all significantly increased if rhIGF-I (5 micrograms injected IP every day for 28 days) was concurrently administered with AZT. Additionally, when mice were initially myelosuppressed by several weeks of AZT treatment, the subsequent administration of rhIGF-I resulted in an increase in hematopoietic progenitor cell content. No significant pathologic effects or weight changes were observed in mice receiving repeated injections of rhIGF-I at this dose and schedule. Thus, rhIGF-I exerts hematopoietic growth-promoting effects in vivo and may be of potential clinical use in promoting hematopoiesis in the face of myelotoxic therapy.
Laboratory of Leukocyte Biology, National Cancer Institute-Frederick Cancer Research and Development Center, MD 21702-1201.
G
G
Tsarfaty
D L
DL
Longo
W J
WJ
Murphy
D000818:Animals; D001854:Bone Marrow Cells; D003114:Colony-Forming Units Assay; D013006:Growth Hormone / Q000494:pharmacology; D006410:Hematopoiesis / Q000187:drug effects*; D006412:Hematopoietic Stem Cells / Q000166:cytology; D007334:Insulin-Like Growth Factor I / Q000494:pharmacology*; D051379:Mice; D008810:Mice, Inbred C57BL; D016513:Mice, SCID; D011994:Recombinant Proteins; D013154:Spleen / Q000166:cytology; D015215:Zidovudine / Q000037:antagonists & inhibitors
D011994:Recombinant Proteins; D015215:Zidovudine; D007334:Insulin-Like Growth Factor I; D013006:Growth Hormone