Single oral dose of prednisone decreases leukotriene B 4 production by alveolar macrophages from patients with nocturnal asthma but not control subjects: Relationship to changes in cellular influx and FEV 1

Abstract

Background: 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. Objective: This study was designed to determine the effect of prednisone on pulmonary alveolar macrophage production of leukotriene B 2 and thromboxane B 2 at night and how it relates to changes in pulmonary function and cellular influx. Methods: 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. Results: Patients with nocturnal asthma had both a significantly greater fall in forced expiratory volume in 1 second (FEV 1) 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 LTB 4 production during placebo administration in the three groups. After prednisone treatment, there was an improvement in the nocturnal fall in FEV 1 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 LTB 4 production in patients with nocturnal asthma compared with a small increase in both patients with nonnocturnal asthma and normal subjects. Thromboxane B 2 production did not change. The decrease in LTB 4 production was correlated with the fall in granulocytic cells and improvement in the nocturnal FEV 1. However, the two variables with the greatest combined influence on the improvement in FEV 1 were the decrease in stimulated LTB 4 production and the fall in neutrophil influx. Conclusions: We demonstrate for the first time that a single oral dose of prednisone decreases LTB 4 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.