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 (IF) injections of 5 mu g 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 mu g 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.