Lung inflammation in hyperoxia can be prevented by antichemokine treatmentin newborn rats

Hyperoxia may contribute to lung disease in newborns through effects on alv eolar neutrophils which predominate in respiratory distress syndrome and ot her acute lung injuries. Neutrophil chemokines such as interleukin-8 (IL-8) regulate chemoattraction, and are elevated in tracheal aspirates of newbor ns who develop bronchopulmonary dysplasia (BPD). Blockade of neutrophil che mokines may reduce hyperoxia-induced inflammatory lung injury and BPD. We t herefore tested the hypothesis that hyperoxia contributes to elevations of rat neutrophil chemokines, cytokine-induced neutrophil chemoattractant-1 (C INC-1), and macrophage inflammatory protein-2 (MIP-2) in newborn rat lung. Newborn rats were exposed to air or 95% O-2 far 8 d. CINC-1 and MIP-2 were measured in whole lung homogenates by ELISA. Newborn 95% O-2-exposed animal s were given anti-CINC-1 or anti-MIP-2 1, 5, or 10 mug on Days 3 and 4 of 9 5% O-2 exposure. Bronchoalveolar ravage (BAL) was performed after perfusion on Day 6 to evaluate airway neutrophils, and myeloperoxidase (MPO) was mea sured in perfused whole lung. Lungs were examined histologically and immuno histochemically for effects of 95% O-2 +/- antichemokine. CINC-1 and MIP-2 increased nearly tenfold by Day 8 95% O-2 treatment versus air control. CIN C-1 and MIP-2 immunolabeling was increased in alveolar macrophages and alve olar epithelium in 95% O-2. Anti-CINC-1 and anti-MIP-2 treatment at every d ose reduced neutrophil number > 90% in BAL. Anti-CINC-1 10 mug reduced tiss ue MPO by 50%. Antichemokine treatment on Days 3 and 4 prevented alveolar s eptal thickening and reduced chemokine immunolabeling on Day 6. Hyperoxia-i nduced neutrophil influx is mediated in part by CINC-1 and MIP-2 in newborn rats and can be partially prevented by treatment with anti-CINC-1 and anti -MIP-2.