Caffeine enhances sodium influx and sodium‐linked fluid transport in respiratory epithelium

Abstract

Caffeine minimizes the time on assisted ventilation in premature infants, possibly as a result of an effect on central respiratory drive. Alternatively, we considered that caffeine improves outcome as a result of improved lung water balance. To test this notion, we studied the effect of caffeine on ion transport in cultured lung cells. We treated an immortal lung epithelial cell line (A549) and distal lung epithelial cells from fetal sheep (FDLE) with caffeine (10−5 M) for 24 h and measured the accumulation of 22Na through pathways that are inhibited by amiloride. Caffeine increased the fraction of amiloride‐sensitive Na uptake by 25% in both cell lines (A549: control 214 ± 51 v caffeine 282 ± 133; FDLE: control 126 ± 29 v caffeine 150 ± 48 nmol/mg protein/5 min, P < 0.05). To study the associated change in fluid movement, we grew the cells on a semi‐permeable surface and measured the change in protein concentration in the supernatant as an index of fluid movement across the monolayer. Caffeine treatment as above increased fluid clearance by 30% (A549: control 106 ± 29 v caffeine 137 ± 26; FDLE: control 79 ± 29 v caffeine 106 ± 30 μL/24h, P < 0.05), an effect that was inhibited in the presence of amiloride (A549: control 61 ± 24 v caffeine 69 ± 25; FDLE: control 103 ± 14 v caffeine 109 ± 16 μL/24h). Our results indicate caffeine increases transepithelial sodium reabsorption and fluid movement through amiloride‐sensitive pathways. We speculate that the beneficial effect of caffeine on respiratory function in the premature lung may be, at least in part, a result of an improvement in lung water balance.