Interleukin-1 Balance in the Lungs of Preterm Infants Who Develop Bronchopulmonary Dysplasia

<i>Background:</i> The local pulmonary balance between the agonist and antagonist of interleukin-1 (IL-1) may influence the development of inflammatory disease and resultant structural damage in a variety of human diseases including adult respiratory distress syndrome and asthma. <i>Objectives:</i> We tested the hypothesis that IL-1 cytokines are early markers for bronchopulmonary dysplasia (BPD), when measured in tracheal aspirates (TAs) obtained from premature infants being ventilated for respiratory distress syndrome during the first week of life. <i>Methods:</i> Serial TAs were collected on days 1, 3, 5 and 7 from 35 preterm infants (16 BPD, 19 non-BPD) in the absence of chorioamnionitis, and were assayed for IL-1 cytokines and leukocytes. <i>Results:</i> In spite of comparable maternal demographic and clinical characteristics, premature infants who developed BPD had higher levels of IL-1 receptor antagonist (Ra) in their airways on the first day of life. This antagonist IL-1Ra was an early and persistent marker for BPD during the first week of life. The agonist IL-1β also increased significantly for BPD patients early, both compared to non-BPD patients, and also within the BPD group. While the early (day 1) IL-1 antagonist/agonist molar balance offered protection, by days 5 and 7, a threshold for IL-1Ra in the presence of increasing IL-1β expression-favored pro-inflammation in the BPD group. <i>Conclusions:</i> We conclude that a strong and early expression of airway antagonist (IL-1Ra) proves ultimately to be sub-optimal and non-protective due to the robust expression of airway agonist (IL-1β) seen by day 5 in premature infants who develop BPD.