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)

Background: Nocturnal worsening of asthma is associated,vith an increa se bl numbers of airway inflammatory cells during the early morning. H owever, cell function during the night, with and without administratio n of steroids, has not been investigated Objective: This study was des igned to determine the effect of prednisone on pulmonary alveolar macr ophage production of leukotriene B-2 and thromborane B-2 at night and how it relates to changes in pulmonary function and cellular influx. M ethods: Alveolar macrophages were obtained from patients with nocturna l asthma, patients with nonnocturnal asthma, and normal control subjec ts at 4:00 AM by bronchoalveolar lavage after administration of placeb o and prednisone. Cells were placed in limited cell culture and eicosa noids were measured from baseline and stimulated cells. Results: Patie nts with nocturnal asthma had both a significantly greater fall in for ced expiratory volume in 1 second (FEV(1)) and a greater influx of neu trophils 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) p roduction during placebo administration in the three groups. After pre dnisone treatment there was an improvement in the nocturnal fall in FE V(1) and a significant decrease in the neutrophil influx in patients w ith nocturnal asthma compared with the other groups. These changes wer e accompanied by a significant decrease in the stimulated LTB(4) produ ction in patients with nocturnal asthma compared with a small increase in both patients with nonnocturnal asthma and normal subjects. Thromb oxane 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 com bined influence on the improvement in FEV(1) were the decrease in stim ulated LTB(4) production and die fall in neutrophil influx Conclusions : We demonstrate for the first time that a single oral dose of prednis one decreases LTB(4) production from alveolar macrophages, obtained at night from patients with nocturnal asthma, during a time of known inf lammation. Further, this decrease in stimulated production is associat ed with decreases in cellular influx and improvement in pulmonary func tion.