Anti-neutrophil chemokine preserves alveolar development in hyperoxia-exposed newborn rats

Inflammation may contribute to lung injury and impaired alveolar developmen t in bronchopulmonary dysplasia. We treated hyperoxia-exposed newborn rats with antibodies to the neutrophil chemokine cytokine-induced neutrophil che moattractant-1 (CINC-1) during 95% O-2 exposure to reduce adverse effects o f hyperoxia-induced inflammation on lung development. Rats were exposed at birth to air, 95% O-2, or 95% O-2 + anti-CINC-1 (injected on days 3 and 4). Bromodeoxyuridine (BrdU) was injected 6 h before death. Anti-CINC-1 treatm ent improved weight gain but not survival at day 8. Anti-CINC-1 reduced bro nchoalveolar lavage neutrophils at day 8 to levels equal to air controls. T otal detectable lung CINC-1 was reduced to air control levels. Lung complia nce was improved by anti-CINC-1, achieving air control levels in the 10-mg anti-CINC-1 group. Anti-CINC-1 preserved proliferating cell nuclear antigen expression in airway epithelium despite 95% O-2 exposure. BrdU incorporati on was depressed by hyperoxia but preserved by anti-CINC-1 to levels simila r to air control. Alveolar volume and surface density were decreased by hyp eroxia but preserved by anti-CINC-1 to levels equal to air control. Blockad e of neutrophil influx in newborns may avert early lung injury and avoid al veolar developmental arrest that contributes to bronchopulmonary dysplasia.