Abstrakt: |
Rh granulocyte-macrophage (GM) colony-stimulating factor (CSF) and rh granulocyte (G) CSF have been demonstrated to induce proliferation and maturation of myeloid stem cells and release of mature polymorphonucleocytes (PMNs) from human and animal adult bone marrows. Unfortunately, reduced bone marrow progenitor cells, neutrophil storage pool (NSP) depletion and peripheral neutropenia are characteristic of human and animal newborn bone marrows. We investigated the effect of administering intraperitoneal rhGM-CSF and rhG-CSF to Sprague-Dawley newborn rats (< 36 h). Newborn rats treated with intraperitoneal CSF (3.0 μg/kg) demonstrated significant leukocytosis at 6 and 24 h: rhGM-CSF vs. control, WBC (103/mm3), at 6 h, 8.0 ± 0.5 vs. 4.3 ± 0.9 (p ≤ 0.003), and at 24 h, 7.7 ± 1.7 vs. 3.8 ± 0.2 (p≤ 0.008); rhG-CSF vs. control WBC (103/mm3) at 6 h, 6.6 ± 1.2 vs. 4.3 ± 0.1 (p ≤ 0.03), and at 24 h, 8.1 ± 0.2 vs. 3.75 ± 0.2 (p ≤ 0.003). The absolute neutrophil count was also significantly elevated at 6 h following intraperitoneal CSF (3.0 μg/kg): RhGM-CSF vs. control, 1,827 ± 25 vs. 379 ± 10 (p ≤ 0.001); rhG-CSF vs. control, 1,698 ± 40 vs. 371 ± 10.1 (p ≤ 0.001). Additionally, femurs were surgically removed and flushed with buffer and marrow neutrophil storage pool (NSP; PMN + band + Meta) determined following rhGM-CSF (3.0 μg/kg vs. control) at 6 h: NSP 5.2 ± 1.3 vs. 16 ± 2.4% (p < 0.001), suggesting an association with peripheral neutrophilia at 6 h and NSP egress from the bone marrow. The NSP after 30 h demonstrated no difference between CSF and control. Lastly, marrow neutrophil proliferative pool (Blasts + Pro + Myelo) were determined after intraperitoneal rhG-CSF and GM-CSF and found to be significantly increased 48 h after administration. We postulate that CSFs may promote early leukocytosis and neutrophilia in the newborn rat by inducing NSP egress from the bone marrow, but do not completely exhaust NSP reserves. |