Effects of Therapeutic Recombinant Granulocyte Colony Stimulating Factor

重组人粒细胞集落刺激因子联合E。重组人粒细胞集落刺激因子对循环中性粒细胞数量和功能的影响。在免疫功能低下的患者和动物模型中，给予G-CSF可改善宿主防御并降低与感染相关的发病率。目前尚不清楚G-CSF的治疗性给药对有感染风险或发展为感染风险的免疫功能患者是有益还是有害。在致死性细菌性腹膜炎犬模型中，G-CSF预处理可增加循环中中性粒细胞数量，加速细菌和内毒素清除，改善心血管功能和存活率。在随后的一系列研究中，我们评估了在细菌性脓毒症开始时给予G-CSF的治疗效果，而不是预防性给予的效果。在这些研究中，我们发现，即使在非常高的剂量下给予治疗性G-CSF，也不会导致败血症期间循环中中性粒细胞数量的增加，也没有提供保护优势。这些发现表明，脓毒症相关事件可能直接抑制外源性G-CSF的刺激作用，也可能导致宿主最大的炎症反应，而宿主对外源性G-CSF的影响不敏感。这些研究表明，在出现致死性细菌性脓毒症的患者中，给予G-CSF治疗可能没有什么好处。

The Effects of Therapeutic Recombinant Granulocyte Colony Stimulating Factor with Intraperitoneal E. Recombinant granulocyte colony stimulating factor (G-CSF) increases circulating neutrophil number and function. Administration of G-CSF improves host defense and decreases morbidity associated with infection in immunocompromised patients and animal models. It is unclear whether therapeutic administration of G- CSF will have benefi-cial or harmful effects in immunocompetent patients at risk of or developing infection. We have shown that G-CSF pretreatment in a canine model of lethal bacterial peritonitis increases circulating neutrophil numbers, accelerates bacteria and endotoxin clearance and improves cardiovascular function and survival. In a subsequent set of studies, we evaluated the effects of G-CSF administered therapeutically at the onset of bacterial sepsis rather than prophylactically. In these studies we found that therapeutic G-CSF even if given at very high dosages did not result in increased circulating neutrophil numbers during the septic period and did not offer a protective advantage. These findings suggest that sepsis associated events may either directly inhibit the stimulatory effects of exogenous G-CSF, or alternatively result in a maximal inflammatory response by the host which is insensitive to the effects of exogenous G-CSF. These studies suggest that therapeutic administration of G-CSF in patients presenting with lethal bacterial sepsis may have little benefit.