Tracheal aspirate IL-8 concentration and airway epithelial cell IL-8 expression are each increased in premature infants undergoing mechanical ventilation.We sought to determine the cytokines responsible for IL-8 expression in this context.Tracheal aspirates were collected from 18 mechanically ventilated premature infants.IL-8 protein abundance was high in tracheal aspirates from ventilated premature infants (mean, 5806 ±4923 pg/mL).IL-1α(mean, 20 ±6 pg/mL), IL-1β(mean 67 ±46 pg/mL), and tumor necrosis factor (TNF)-α(mean, 8 ±2 pg/mL) were also found.Incubation of tracheal aspirates with 16HBE14o-human bronchial epithelial cells increased IL-8 protein in both cell lysates and supernatants, as well as transcription from the IL-8 promoter.Aspirates also induced nuclear factor (NF)-κB activation.Mutation of the IL-8 promoter NF-κBsite abolished aspirate-induced IL-8 transcription.Endotoxin concentrations in the tracheal aspirates were negligible and incapable of inducing IL-8 promoter activity.Finally, incubation of tracheal aspirates with a neutralizing antibody against IL-1βreduced epithelial cell IL-8 production, whereas neutralizing antibodies against IL-1αand TNF-αhad no effect.We conclude that airway fluid from mechanically ventilated premature infants contains soluble factors capable of inducing airway epithelial cell IL-8 expression via a NF-κB-dependent pathway, and that IL-1βplays a specific role in this process.
展开▼
