EFFECTS OF DEXAMETHASONE ON CHEMOTACTIC ACTIVITY AND INFLAMMATORY MEDIATORS IN TRACHEOBRONCHIAL ASPIRATES OF PRETERM INFANTS AT RISK FOR CHRONIC LUNG-DISEASE

To evaluate the effects of dexamethasone on pulmonary inflammation and permeability in preterm infants at high risk for chronic lung disease (birth weight <1200 gm), we assessed tracheobronchial aspirate fluid for chemotactic activity and concentrations of mediators of inflammati on. In a prospective study, 21 infants still undergoing mechanical ven tilation at day 10 of postnatal age who required a fraction of inspire d oxygen greater-than-or-equal-to 0.3, a peak inspiratory pressure gre ater-than-or-equal-to 16 cm H2O, or both were randomly assigned to tre atment with dexamethasone at day 10 (early treatment group, n = 10) or day 16 (late treatment group, n = 11). The groups were compared with respect to all measurements on day 15; the late treatment group served as a control group. Additionally, the effects of dexamethasone within both groups were evaluated. In the early treatment group, the chemota ctic response of peripheral blood neutrophils exposed to tracheobronch ial aspirate fluid was significantly reduced 5 days after initiation o f dexamethasone treatment compared with pretreatment values of the lat e treatment group (median (25th to 75th percentile): migratory distanc e before dexamethasone, 149 mum (140 to 173 mum); after dexamethasone, 81 mum (68 to 114 mum); p < 0.01). In addition, the following values were decreased after dexamethasone therapy in the early treatment grou p: number of neutrophils in tracheobronchial aspirate fluid (p < 0.05) , and concentrations of leukotriene B4(P < 0.01), interleukin-1 (p < 0 .01), elastase-alpha1-proteinase inhibitor (p < 0.01), and albumin (p < 0.01). Free elastase activity was found in only two infants; detecta ble activity of protective alpha1-proteinase inhibitor was present in the others. Analysis of dexamethasone effects within the groups showed that all measurements were significantly decreased after both the ear ly and the late treatment regimens, with the exception of leukotriene B4 and interleukin-1, which declined only after early dexamethasone tr eatment. Our results indicate that the pulmonary inflammatory response and microvascular permeability are decreased by dexamethasone, which affects the release of inflammatory mediators and neutrophil influx in to the airways of preterm infants who require mechanical ventilation.