Cairo M S, Plunkett J M, Mauss D, Van de ven C
Division of Hematology-Oncology, Childrens Hospital of Orange County, University of California, Irvine 92668.
Blood. 1990 Nov 1;76(9):1788-94.
Single-pulse administration of rhG-colony-stimulating factor (CSF) to neonatal rats was previously demonstrated to induce peripheral neutrophilia and modulate bone marrow (BM) neutrophil storage and proliferative pools (NSP + NPP). In this study, we investigated the prolonged effects of 7 days of rhG-CSF therapy (5 micrograms/kg/per day). Sprague-Dawley newborn rats (less than or equal to 24 hours) were injected intraperitoneally (IP) (daily for 7 days) with rhG-CSF or phosphate-buffered saline/human serum albumin (PBS/HSA). RhG-CSF induced a significant early and late peripheral neutrophilia: 6,905 +/- 1,625 (day 1) and 9,223 +/- 515 microL (day 7) v 1,275 +/- 90/microL (P less than or equal to .0001). In addition, 7 days of rhG-CSF resulted in a significant increase in the BM NSP: 3,247 +/- 190/microL v 1,677 +/- 339/microL (P less than or equal to .001). There was, however, no depletion or significant change in the BM NPP. Seven days of rhG-CSF also induced a mild increase in BM CFU-GM colony formation (P less than or equal to .01). There was, however, no significant change in liver/spleen CFU-GM colonies or in the CFU-GM proliferative rate in either the BM or liver/spleen cultures. Finally, 7 days of prophylactic rhG-CSF therapy resulted in a synergistic response with antibiotic therapy and significantly modulated the mortality rate during experimental group B streptococcal sepsis (GBS) (100% v 50%) (GvsC) (P less than or equal to .001). Pulse rhG-CSF administered at 6 hours or 18 hours after GBS inoculation, however, failed to act synergistically with antibiotics to improve survival or prevent peripheral neutropenia. This study suggests that 7 days of prophylactic rhG-CSF therapy induces peripheral neutrophilia, myeloid maturation, increases neutrophil BM reserves and also may provide immunologic enhancement of neonatal host defense during experimental GBS in term neonatal rats.
先前已证明，对新生大鼠单次脉冲注射重组人粒细胞集落刺激因子（CSF）可诱导外周血中性粒细胞增多，并调节骨髓（BM）中性粒细胞储存池和增殖池（NSP + NPP）。在本研究中，我们调查了7天重组人粒细胞集落刺激因子治疗（5微克/千克/天）的长期效果。将Sprague-Dawley新生大鼠（小于或等于24小时）腹腔内注射（IP）（每天1次，共7天）重组人粒细胞集落刺激因子或磷酸盐缓冲盐水/人血清白蛋白（PBS/HSA）。重组人粒细胞集落刺激因子诱导了显著的早期和晚期外周血中性粒细胞增多：第1天为6,905±1,625个/微升，第7天为9,223±515个/微升，而对照组为1,275±90个/微升（P≤0.0001）。此外，7天的重组人粒细胞集落刺激因子治疗导致骨髓NSP显著增加：3,247±190个/微升，而对照组为1,677±339个/微升（P≤0.001）。然而，骨髓NPP没有减少或显著变化。7天的重组人粒细胞集落刺激因子治疗还诱导骨髓CFU-GM集落形成轻度增加（P≤0.01）。然而，肝脏/脾脏CFU-GM集落或骨髓及肝脏/脾脏培养物中CFU-GM增殖率没有显著变化。最后，7天的预防性重组人粒细胞集落刺激因子治疗与抗生素治疗产生协同反应，并显著调节了实验组B族链球菌败血症（GBS）期间的死亡率（100%对50%）（G组对C组）（P≤0.001）。然而，在GBS接种后6小时或18小时给予脉冲重组人粒细胞集落刺激因子未能与抗生素产生协同作用以提高存活率或预防外周血中性粒细胞减少。本研究表明，7天的预防性重组人粒细胞集落刺激因子治疗可诱导外周血中性粒细胞增多、髓系成熟，增加中性粒细胞骨髓储备，并且在足月新生大鼠实验性GBS期间可能还会增强新生儿宿主防御的免疫功能。
