Significance HIV infection is associated with multiple hematologic abnormalities including disturbances of regulatory cytokines. This suggests that administration of hematopoietic cytokines that can stimulate hematopoiesis may be useful in overcoming the abnormalities associated with infection, although there is limited evidence to suggest such treatments are efficacious, will not enhance viral replication, or result in adverse effects, particularly during pregnancy. Objectives Studies were conducted to determine whether maternal administration of stem cell factor (SCF, 25 5g/kg/day) + granulocyte-colony stimulating factor (G-CSF, 50 5g/kg/day) can alter maternal and fetal hematopoiesis, increase the likelihood of infection of fetal HSC, and accelerate disease. Studies in adult patients suggest that the frequency of hematopoietic stem cell (HSC) infection is low, however, fetal HSC are known to differ from adults in their cycling rates and because they are a constant and rapidly expanding pool. Results Chronic maternal administration of SCF and G-CSF during the late second-third trimesters resulted in a rapid rise in maternal neutrophil counts in all animals studied. In contrast, SIV-infected fetuses showed little hematopoietic change from the typical features of fetal infection including marked neutropenias. Studies have shown that there is little transport of G-CSF when administered to the dam during gestation, although a marked blunting in the normal rise in fetal neutrophil counts that has previously been shown to occur in noninfected animals was more enhanced in SIV-infected fetuses. Studies are currently in progress to determine if sorted populations of marrow-derived fetal stem cells have an increased likelihood of infection, and if administration of SCF and G-CSF enhances the rate of infection of a specific cell population. Future Directions The role of G-CSF receptor expression at placental and fetal level will be explored, and treatment of SIV-infected gravid and neonatal animals with antiretrovirals in combination with select cytokines will also be investigated. KEYWORDS pregnancy, hematopoiesis, stem cells, fetus, SCF, G-CSF, SIV;
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