Stimulation of fetal granulopoiesis by intrauterine injection of recombinant human granulocyte colony-stimulating factor into rat fetuses

The small neutrophil reserve and exaggerated release of stored neutrophils are factors which predispose neonates to neutrophil reserve exhaustion duri ng bacterial sepsis. Our objective is to try to improve in utero the myelop oietic function of the fetus before delivery. In the first series, recombin ant human (rh) granulocyte colony-stimulating factor(G-CSF) (rhG-CSF; 100 m u g/kg) was injected subcutaneously into rat fetuses at the indicated times to assess drug absorption and fetal response. In the second series, rhG-CS F (100 mu g/kg) or saline (control) was injected into the fetuses once ever y other day to investigate the effect of repeated injections of rhG-CSF on enhancing fetal myelopoiesis preceding birth. Delivery was performed by ces arean section on embryonic day 21. The plasma concentration of G-CSF was de termined by ELISA. The effect of rhG-CSF injection on granulopoiesis was as sessed by measurement of the neutrophil count in the fetal peripheral blood and by histological examination of the fetal bone marrow, spleen, and live r. Fetally administered rhG-CSF enhanced fetal myelopoiesis preceding birth .