Abstract
In order to elucidate the therapeutic mechanisms of low dose-long term erythromycin (EM) therapy in patients with diffuse panbronchiolitis (DPB), the authors evaluated the effect of in vitro EM treatment on neutrophil (PMN) oxygen radicals production. EM has potent capacity to suppress PMN chemiluminescence (CL) induced by the N-formyl Met-leu-phe (FMLP), opsonized zymosan, and calcium ionophore A23187 stimulation. In marked contrast, phorbol myristate acetate (PMA)-induced PMN CL were much less affected by EM treatment. The suppressive activity of EM was dependent on the EM concentration and at a EM concentration of 25μg/ml, FMLP-induced PMN CL were suppressed by 45.3±5.6% (n=7), but PMA-induced CL were suppressed only marginally, 11.9±3.7% (n=7). The onset of inhibitory activity of EM is rapid and at 5min., 60.1% of the maximum suppression at 60 min. was observed. This EM-induced suppression was found to be reversible and dependent on the EM-pretreatment temperature since the suppressive activity of EM were observed only at 37°C but not at 0°C.These results suggest that actively transported intracellular EM exerts its suppressive activity by inhibiting the process of Ca++ transfer or Ca++ utilization by cells. In addition, these results were consistent with the concept that EM might act as an anti-inflammatory agent in chronic bacterial airway infections such as bronchiectasis and DPB where the PMN appear to play an important role in the generation of airway destruction.
