Recombinant GM-CSF reduces lung injury and mortality during neutropenic Candida sepsis.
Recombinant GM-CSF reduces lung injury and mortality during neutropenic Candida sepsis.
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重组 GM-CSF 可减少中性粒细胞减少性念珠菌败血症期间的肺损伤和死亡率。
DOI：
10.1152/ajplung.1994.266.5.l561
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发表时间：
1994
期刊：
影响因子：
--
通讯作者：
Matuschak,GM
中科院分区：
文献类型：
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作者：
Lechner,AJ;Lamprech,KE;Potthoff,LH;Tredway,TL;Matuschak,GM
环磷酰胺（CY）诱导的中性粒细胞减少症加剧了清醒大鼠白念珠菌（CA）真菌血症期间的感染性休克和急性肺损伤。我们假设，这些动物与重组鼠粒细胞-巨噬细胞集落刺激因子（GM-CSF）的治疗，提高宿主防御播散性念珠菌病通过增加外周中性粒细胞（PMN）和增强内源性抗真菌细胞因子，包括肿瘤坏死因子-α（TNF）的生产。用10（7）酵母相CA感染未处理（嗜中性粒细胞充满）或血小板减少大鼠;从CA感染前3天开始，亚组接受GM-CSF（25 μ g/kg sc）或无菌0.9% NaCl（NS），每天两次。动脉血流动力学，形成的血液元素，血清和支气管肺泡灌洗液（BALF）中的生物活性TNF，和肺组织病理学进行了监测长达72小时后感染。所有接受GM-CSF的幼稚动物（n = 5）和78%接受NS的幼稚大鼠（n = 9）在72小时内保持正常血压，无肺损伤，主要区别在于CA感染前的基线PMN（8.8 +/- 1.8 x 10（3）/微升，平均值+/- SE，对比3.7 +/- 0.4 x 10（3）/微升，P < 0.01）。中性粒细胞减少大鼠给予NS（基线PMN = 41 +/- 10/微升，n = 7）致敏CA，100%死于低温休克与严重呼吸窘迫56小时内感染。肺动脉周围和肺泡出血突出。尽管GM-CSF在感染开始时没有增加CY动物的基线PMN（162 +/- 58/μ l，n = 8），但这些大鼠中有62%在72小时内保持正常血压和正常呼吸（P < 0.01），并且它们的肺没有显示血管周围出血、肺泡破裂或真菌。（250字处删节）
Cyclophosphamide (CY)-induced neutropenia exacerbates septic shock and acute lung injury during Candida albicans (CA) fungemia in conscious rats. We hypothesized that treatment of such animals with recombinant murine granulocyte-macrophage colony-stimulating factor (GM-CSF) improves host defense during disseminated candidiasis by increasing peripheral neutrophils (PMNs) and enhancing endogenous production of antifungal cytokines including tumor necrosis factor-alpha (TNF). Naive (neutrophil-replete) or neutropenic rats were infected with 10(7) yeast-phase CA; subgroups received GM-CSF (25 micrograms/kg sc) or sterile 0.9% NaCl (NS) twice a day beginning 3 days before CA infection. Arterial hemodynamics, formed blood elements, bioactive TNF in serum and bronchoalveolar lavage fluid (BALF), and lung histopathology were monitored for up to 72 h after infection. All naive animals receiving GM-CSF (n = 5) and 78% of naive rats given NS (n = 9) remained normotensive through 72 h with no lung injury, differing principally in baseline PMNs before CA infection (8.8 +/- 1.8 x 10(3)/microliters, mean +/- SE, vs. 3.7 +/- 0.4 x 10(3)/microliters, respectively, P < 0.01). Neutropenic rats given NS (baseline PMN = 41 +/- 10/microliters, n = 7) were sensitized to CA, and 100% died of hypothermic shock with severe respiratory distress within 56 h of infection. Pulmonary periarterial and alveolar hemorrhage were prominent. Although GM-CSF did not increase baseline PMNs in CY animals by the outset of infection (162 +/- 58/microliters, n = 8), 62% of these rats remained normotensive and eupneic through 72 h (P < 0.01), and their lungs showed no perivascular hemorrhage, alveolar disruption, or fungi.(ABSTRACT TRUNCATED AT 250 WORDS)