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

Am J Respir Crit Care Med. 2000 Dec;162(6):2316-23. doi: 10.1164/ajrccm.162.6.9911020.


Hyperoxia may contribute to lung disease in newborns through effects on alveolar neutrophils which predominate in respiratory distress syndrome and other acute lung injuries. Neutrophil chemokines such as interleukin-8 (IL-8) regulate chemoattraction, and are elevated in tracheal aspirates of newborns who develop bronchopulmonary dysplasia (BPD). Blockade of neutrophil chemokines may reduce hyperoxia-induced inflammatory lung injury and BPD. We therefore tested the hypothesis that hyperoxia contributes to elevations of rat neutrophil chemokines, cytokine-induced neutrophil chemoattractant-1 (CINC-1), and macrophage inflammatory protein-2 (MIP-2) in newborn rat lung. Newborn rats were exposed to air or 95% O(2) for 8 d. CINC-1 and MIP-2 were measured in whole lung homogenates by ELISA. Newborn 95% O(2)-exposed animals were given anti-CINC-1 or anti-MIP-2, 1, 5, or 10 microg on Days 3 and 4 of 95% O(2) exposure. Bronchoalveolar lavage (BAL) was performed after perfusion on day 6 to evaluate airway neutrophils, and myeloperoxidase (MPO) was measured in perfused whole lung. Lungs were examined histologically and immunohistochemically 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. CINC-1 and MIP-2 immunolabeling was increased in alveolar macrophages and alveolar epithelium in 95% O(2). Anti-CINC-1 and anti-MIP-2 treatment at every dose reduced neutrophil number > 90% in BAL. Anti-CINC-1 10 microg reduced tissue MPO by 50%. Antichemokine treatment on days 3 and 4 prevented alveolar septal thickening and reduced chemokine immunolabeling on Day 6. Hyperoxia-induced 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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acute Disease
  • Analysis of Variance
  • Animals
  • Animals, Newborn
  • Bronchopulmonary Dysplasia / etiology
  • Bronchopulmonary Dysplasia / metabolism
  • Bronchopulmonary Dysplasia / prevention & control
  • Chemokine CXCL1
  • Chemokine CXCL2
  • Chemokines, CXC / antagonists & inhibitors*
  • Chemokines, CXC / metabolism
  • Chemotactic Factors / antagonists & inhibitors*
  • Chemotactic Factors / metabolism
  • Dose-Response Relationship, Drug
  • Growth Substances / metabolism
  • Humans
  • Hyperoxia / complications
  • Hyperoxia / drug therapy*
  • Hyperoxia / metabolism
  • Immunohistochemistry
  • Infant, Newborn
  • Intercellular Signaling Peptides and Proteins*
  • Lung / chemistry
  • Lung / metabolism
  • Lung / pathology
  • Monokines / antagonists & inhibitors*
  • Monokines / metabolism
  • Neutrophils / metabolism
  • Pneumonia / etiology
  • Pneumonia / metabolism
  • Pneumonia / prevention & control*
  • Random Allocation
  • Rats
  • Time Factors


  • CXCL1 protein, human
  • Chemokine CXCL1
  • Chemokine CXCL2
  • Chemokines, CXC
  • Chemotactic Factors
  • Cxcl1 protein, rat
  • Cxcl2 protein, rat
  • Growth Substances
  • Intercellular Signaling Peptides and Proteins
  • Monokines