EARLY PRODUCTION OF MACROPHAGE INFLAMMATORY PROTEIN-1-ALPHA OCCURS INRESPIRATORY-DISTRESS SYNDROME AND IS ASSOCIATED WITH POOR OUTCOME

Although progression to pulmonary fibrosis in preterm infants with res piratory distress syndrome (RDS) is related to the inflammatory respon se, the nature of this response remains controversial. We have therefo re performed sequential bronchoalveolar lavages in 30 infants with RDS (13 of whom developed bronchopulmonary dysplasia) and 7 ventilated co ntrol infants, characterizing the cells obtained by immunohistochemica l analysis of lineage-specific markers and assaying macrophage-associa ted chemokines and cytokines in supernatant fluid. At all ages from bi rth, lavage supernatants demonstrated highly significant increase over controls of the beta-chemokine macrophage inflammatory protein (MIP)- 1 alpha, although not of regulated upon activation, normal T cell expr essed and secreted (RANTES), of the cytokines tumor necrosis factor (T NF)-alpha and IL-1 beta, and of elastase/alpha-1 antitrypsin. Signific antly higher concentrations of MIP-1 alpha in particular were associat ed with the later development of fibrosis. Increased numbers of macrop hages expressing the activation marker RM/3-1 were found at all ages i n bronchopulmonary dysplasic infants, whereas neutrophil numbers were increased from d 3. Dexamethasone administered to 10 infants induced r apid decrease in inflammatory cell numbers and concentrations of MIP-1 alpha, tumor necrosis factor-alpha, IL-1 beta, and elastase/alpha-1 a ntitrypsin. The inflammatory response in neonatal RDS begins within th e first day of life. Long-term outcome is associated with the magnitud e of this early response, in particular production of MIP-1 alpha The early introduction of specific therapy is thus likely to be beneficial .