Stimulation of ciliary activity by indomethacin in rabbit tracheal epithelial organ culture

Inflammatory mediators influence mucociliary transport function in the lung, which may be dependent on the beating of the underlying cilia. To determine whether a nonsteroidal anti-inflammatory drug affects this function, and, if so, what is the mechanism action, we examined the effect of indomethacin on ciliary beat frequency (CBF) of cultured rabbit tracheal epithelial cells by a photoelectric technique. Addition of indomethacin dose-dependently enhanced CBF without any ciliary discoordination, the maximal increase and Km being 26.5 +/- 4.8% (mean +/- SE, p less than 0.001) and 6.8 X 10(-7) M, respectively. Pretreatment of tissues with nordihydroguaretic acid (10(-5) M), an inhibitor of the lipoxygenase pathway, did not change the baseline CBF, but inhibited the response of CBF to 3 X 10(-6) M indomethacin (p less than 0.01). These results suggest that indomethacin may accelerate mucociliary clearance through the augmentation of ciliary motility and that this ciliostimulation may be mediated by leukotrienes produced by activation of the lipoxygenase pathway of arachidonic acid metabolism.