Wenzel S E, Trudeau J B, Westcott J Y, Beam W R, Martin R J
National Jewish Center for Immunology and Respiratory Medicine, Denver, CO 80206.
J Allergy Clin Immunol. 1994 Nov;94(5):870-81. doi: 10.1016/0091-6749(94)90155-4.
Nocturnal worsening of asthma is associated with an increase in numbers of airway inflammatory cells during the early morning. However, cell function during the night, with and without administration of steroids, has not been investigated.
This study was designed to determine the effect of prednisone on pulmonary alveolar macrophage production of leukotriene B2 and thromboxane B2 at night and how it relates to changes in pulmonary function and cellular influx.
Alveolar macrophages were obtained from patients with nocturnal asthma, patients with nonnocturnal asthma, and normal control subjects at 4:00 AM by bronchoalveolar lavage after administration of placebo and prednisone. Cells were placed in limited cell culture, and eicosanoids were measured from baseline and stimulated cells.
Patients with nocturnal asthma had both a significantly greater fall in forced expiratory volume in 1 second (FEV1) and a greater influx of neutrophils and eosinophils at 4:00 AM than normal subjects after placebo treatment, whereas patients with nonnocturnal asthma had intermediary responses. There was no difference in baseline or stimulated LTB4 production during placebo administration in the three groups. After prednisone treatment, there was an improvement in the nocturnal fall in FEV1 and a significant decrease in the neutrophil influx in patients with nocturnal asthma compared with the other groups. These changes were accompanied by a significant decrease in the stimulated LTB4 production in patients with nocturnal asthma compared with a small increase in both patients with nonnocturnal asthma and normal subjects. Thromboxane B2 production did not change. The decrease in LTB4 production was correlated with the fall in granulocytic cells and improvement in the nocturnal FEV1. However, the two variables with the greatest combined influence on the improvement in FEV1 were the decrease in stimulated LTB4 production and the fall in neutrophil influx.
We demonstrate for the first time that a single oral dose of prednisone decreases LTB4 production from alveolar macrophages, obtained at night from patients with nocturnal asthma, during a time of known inflammation. Further, this decrease in stimulated production is associated with decreases in cellular influx and improvement in pulmonary function.
哮喘夜间病情加重与清晨气道炎症细胞数量增加有关。然而，尚未研究夜间使用和不使用类固醇时细胞的功能。
本研究旨在确定泼尼松对夜间肺泡巨噬细胞白三烯B2和血栓素B2产生的影响，以及其与肺功能和细胞流入变化的关系。
在给予安慰剂和泼尼松后，于凌晨4点通过支气管肺泡灌洗从夜间哮喘患者、非夜间哮喘患者和正常对照受试者获取肺泡巨噬细胞。将细胞置于有限细胞培养中，从基线和刺激后的细胞中测量类花生酸。
与安慰剂治疗后的正常受试者相比，夜间哮喘患者在凌晨4点时1秒用力呼气量（FEV1）下降幅度明显更大，中性粒细胞和嗜酸性粒细胞流入量也更大，而非夜间哮喘患者的反应介于两者之间。三组在安慰剂给药期间基线或刺激后的白三烯B₄产生无差异。与其他组相比，泼尼松治疗后，夜间哮喘患者的FEV1夜间下降有所改善，中性粒细胞流入量显著减少。这些变化伴随着夜间哮喘患者刺激后的白三烯B₄产生显著减少，而非夜间哮喘患者和正常受试者均有小幅增加。血栓素B2产生未改变。白三烯B₄产生的减少与粒细胞数量下降和夜间FEV1改善相关。然而，对FEV1改善综合影响最大的两个变量是刺激后的白三烯B₄产生减少和中性粒细胞流入量下降。
我们首次证明，单次口服泼尼松可降低夜间从夜间哮喘患者获取的肺泡巨噬细胞在已知炎症期间白三烯B₄的产生。此外，刺激产生的这种减少与细胞流入减少和肺功能改善有关。
