Effect of granulocyte colony-stimulating factor on systemic and pulmonary responses to endotoxin in pigs.

Effect of granulocyte colony-stimulating factor on systemic and pulmonary responses to endotoxin in pigs.
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粒细胞集落刺激因子对猪内毒素全身和肺部反应的影响。

DOI:
10.1097/00005373-199304000-00015
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发表时间:
1993
期刊:
The Journal of trauma
影响因子:
--
通讯作者:
Bellelsle,JM
Bellelsle,JM
中科院分区:
--
文献类型:
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作者:
Fink,MP;O'Sullivan,BP;Menconi,MJ;Wollert,SP;Wang,H;Youssef,ME;Bellelsle,JM

文献摘要

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粒细胞集落刺激因子 (G-CSF) 刺激中性粒细胞 (PMN) 的产生和功能。在感染实验模型中,对非中性粒细胞减少动物施用 G-CSF 已被证明可以提高存活率,但 PMN 被认为是脂多糖 (LPS) 或菌血症诱导的急性肺损伤的介质。因此,G-CSF 诱导的中性粒细胞增多可能对脓毒症有害。为了研究这种可能性,我们研究了四组猪:G+ E50(n=6)用重组牛(rb)G-CSF(5μg/kg/天)预处理5天,然后用LPS(50μg/kg)攻击; NS+E50(n=6)同样用盐水预处理并用LPS(50μg/kg)攻击; E250(n=6)未经预处理并输注较大剂量的LPS(250μg/kg); RL (n=7) 是输注乳酸林格氏溶液的对照。 rbG-CSF 预处理使外周绝对中性粒细胞计数增加约五倍(与 RL 组相比,p<0.05)。 NS+ E50 和 G+ E50 组的比较表明,rhG-CSF 预处理不会影响 LPS 诱导的平均动脉血压或动脉氧合的变化。这两组的肺损伤指数也相似,尽管 E250 组的肺水肿和蛋白质渗漏到肺泡中较多。我们得出的结论是,G-CSF 诱导的中性粒细胞增多不会对猪对 LPS 的生理反应产生不利影响。
Granulocyte colony-stimulating factor (G-CSF) stimulates the production and function of neutrophils (PMNs). Administration of G-CSF to non-neutropenic animals has been shown to improve survival in experimental models of infection, but PMNs have been implicated as mediators of acute lung injury induced by lipopolysaccharide (LPS) or bacteremia. Thus G-CSF-induced neutrophilia might be deleterious in sepsis. To investigate this possibility, we studied four groups of pigs: G+ E50 (n= 6) were pretreated for 5 days with recombinant bovine (rb) G-CSF (5 [mu] g/kg/day) and then challenged with LPS (50 [mu] g/kg); NS+ E50 (n= 6) were similarly pretreated with saline and challenged with LPS (50 [mu] g/kg); E250 (n= 6) were not pretreated and were infused with a larger dose of LPS (250 [mu] g/kg); RL (n= 7) were controls infused with lactated Ringer's solution. Pretreatment with rbG-CSF increased the peripheral absolute neutrophil count approximately fivefold (p< 0.05 vs. RL group). Comparisons of the NS+ E50 and G+ E50 groups showed that pretreatment with rhG-CSF did not affect LPS-induced alterations in mean arterial blood pressure or arterial oxygenation. Indices of pulmonary injury also were similar in these two groups, although pulmonary edema and protein leakage into alveoli were greater in the E250 group. We conclude that G-CSF-induced neutrophilia does not adversely effect physiologic responses to LPS in pigs.