Azoulay Elie, Attalah Habiba, Yang Kun, Herigault Sabine, Jouault Hélène, Brun-Buisson Christian, Brochard Laurent, Harf Alain, Schlemmer Benoît, Delclaux Christophe
Inserm U 492, Faculté de Médecine-Université Paris XII, Cretiel, France.
Crit Care Med. 2003 Jan;31(1):157-65. doi: 10.1097/00003246-200301000-00025.
Neutropenia recovery may be associated with an increased risk of respiratory function deterioration. A history of pneumonia complicating neutropenia has been identified as the leading cause of adult respiratory distress syndrome during neutropenia recovery in patients receiving anticancer chemotherapy, suggesting that neutropenia recovery may worsen prior lung injury.
Controlled animal study.
Research laboratory of an academic institution.
Male Sprague-Dawley rats.
We studied the effect of recovery from cyclophosphamide-induced neutropenia on endotoxin (lipopolysaccharide)- or hydrochloric acid-induced acute lung injury in rats. We also studied the effects of adding granulocyte colony-stimulating factor.
Compared with noncyclophosphamide-treated rats, rats undergoing neutropenia recovery had a higher wet/dry lung weight ratio after hydrochloric acid-induced but not lipopolysaccharide-induced acute lung injury. Granulocyte colony-stimulating factor significantly increased both alveolar cell recruitment (bronchoalveolar lavage fluid counts) and pulmonary edema (wet/dry lung ratio) in both acute lung injury models during neutropenia recovery. Furthermore, in an experiment in hydrochloric acid-instilled rats, exacerbation by granulocyte colony-stimulating factor of hydrochloric acid-induced acute lung injury was inhibited by lidocaine, which prevents adhesion of neutrophils to endothelial cells. Tumor necrosis factor-alpha and interleukin-1 beta concentrations in supernatants of lipopolysaccharide-stimulated alveolar macrophages from rats undergoing neutropenia recovery with granulocyte colony-stimulating factor treatment were significantly increased compared with rats undergoing neutropenia recovery without granulocyte colony-stimulating factor.
Neutropenia recovery can worsen acute lung injury, and this effect is exacerbated by granulocyte colony-stimulating factor.
中性粒细胞减少症的恢复可能与呼吸功能恶化风险增加有关。在接受抗癌化疗的患者中性粒细胞减少症恢复期，肺炎合并中性粒细胞减少症已被确定为成人呼吸窘迫综合征的主要原因，这表明中性粒细胞减少症的恢复可能会使先前的肺损伤恶化。
对照动物研究。
一所学术机构的研究实验室。
雄性Sprague-Dawley大鼠。
我们研究了环磷酰胺诱导的中性粒细胞减少症恢复对大鼠内毒素（脂多糖）或盐酸诱导的急性肺损伤的影响。我们还研究了添加粒细胞集落刺激因子的效果。
与未用环磷酰胺处理的大鼠相比，经历中性粒细胞减少症恢复的大鼠在盐酸诱导而非脂多糖诱导的急性肺损伤后，肺湿/干重比更高。在中性粒细胞减少症恢复期间的两种急性肺损伤模型中，粒细胞集落刺激因子均显著增加了肺泡细胞募集（支气管肺泡灌洗计数）和肺水肿（肺湿/干比）。此外，在盐酸注入大鼠的实验中，利多卡因抑制了粒细胞集落刺激因子对盐酸诱导的急性肺损伤的加重作用，利多卡因可防止中性粒细胞与内皮细胞黏附。与未用粒细胞集落刺激因子治疗而经历中性粒细胞减少症恢复的大鼠相比，用粒细胞集落刺激因子治疗的经历中性粒细胞减少症恢复的大鼠，脂多糖刺激的肺泡巨噬细胞上清液中的肿瘤坏死因子-α和白细胞介素-1β浓度显著增加。
中性粒细胞减少症的恢复会使急性肺损伤恶化，粒细胞集落刺激因子会加剧这种作用。
