Continuous subcutaneous injection reduces polymorphonuclear leukocyte activation by granulocyte colony-stimulating factor.
Continuous subcutaneous injection reduces polymorphonuclear leukocyte activation by granulocyte colony-stimulating factor.
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DOI：
10.1152/ajplung.00248.2003
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发表时间：
2004
期刊：
影响因子：
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通讯作者：
Yukio Sato;Y. Goto;Shoko Sato;S. Endo;Y. Sohara
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作者：
Yukio Sato;Y. Goto;Shoko Sato;S. Endo;Y. Sohara
粒细胞集落刺激因子（G-CSF）用于中性粒细胞减少症的恢复已经建立；然而，由g - csf诱导的多形核白细胞（PMN）活化引起的急性肺损伤是一种严重的并发症。本研究旨在比较单次给药和连续给药G-CSF对PMN的激活。健康志愿者（年龄33.8 +/- 1.4岁，n = 6）接受单次注射50微米/平方米G-CSF （SI, n = 6）或连续皮下注射50微米/平方米G-CSF 24小时（CI, n = 6），并随访48小时。测量循环白细胞计数、PMN活化标志物、G-CSF、IL-6和PMN弹性酶的循环水平。SI快速升高血清G-CSF水平，在4 h达到峰值，而CI逐渐升高血清G-CSF水平，并在8 ~ 24 h保持稳定。SI使PMN计数在0.5 h迅速下降，在12 h持续升高至峰值，CI使PMN计数逐渐升高，在24 h达到峰值，但两组间的峰值差异不显著。si诱导PMN活化，表现为CD11b表达增加，l -选择素表达减少，f -肌动蛋白含量增加，导致血清IL-6和PMN弹性酶水平升高。这些变化均随CI减弱（P < 0.05）。我们得出结论，连续皮下注射G-CSF导致骨髓反应类似于单次注射，但产生减少的PMN激活。
The use of granulocyte colony stimulating factor (G-CSF) for recovery from neutropenia has been established; however, acute lung injury due to G-CSF-induced polymorphonuclear leukocyte (PMN) activation is a serious complication. This study was designed to compare the activation of PMN with single bolus administration and continuous administration of G-CSF. Healthy volunteers (age 33.8 +/- 1.4 yr; n = 6) received a single bolus injection of 50 microm/m2 of G-CSF (SI; n = 6) or continuous subcutaneous injection of 50 microm/m2 of G-CSF for 24 h (CI; n = 6) and were followed for 48 h. Circulating leukocyte counts, markers of activation on PMN, and circulating levels of G-CSF, IL-6, and PMN elastase were measured. SI rapidly increased serum G-CSF levels, which peaked at 4 h, whereas CI gradually increased G-CSF levels, which remained at a steady level from 8 to 24 h. SI caused a rapid decrease in PMN counts at 0.5 h followed by sustained increase to peak at 12 h. CI gradually increased PMN counts, which peaked at 24 h, but the peak values were not significantly different between the groups. SI-induced activation of PMN, which was characterized by increased expression of CD11b, decreased expression of L-selectin, and increased F-actin content, led to increases in serum IL-6 and PMN elastase level. Such changes were all attenuated with CI (P < 0.05). We conclude that continuous subcutaneous injection of G-CSF resulted in a marrow response similar to that to a single injection but yielded reduced PMN activation.