Association of increased pulmonary interleukin-6 with the priming effect of intra-amniotic lipopolysaccharide on hyperoxic lung injury in a rat model of bronchopulmonary dysplasia.

BACKGROUND

The authors previously demonstrated the priming effect of intra-amniotic lipopolysaccharide (LPS) on hyperoxic lung injury in a rat model of bronchopulmonary dysplasia (BPD).

OBJECTIVES

To investigate the mechanism underlying this priming effect by determining biochemical profiles in a rat model of BPD.

METHODS

The rat model involved intra-amniotic LPS administration and postnatal hyperoxia (85%). The mRNA expressions of interleukin-6 (IL-6), vascular endothelial growth factor (VEGF), VEGF receptor-2 (VEGFR-2), basic fibroblast growth factor (bFGF), and transforming growth factor beta(1) (TGF-beta(1)), as well as the protein levels of IL-6, VEGF, and protein carbonyl in lung tissue were compared between the LPS plus hyperoxia, the LPS only, the hyperoxia only, and the control groups.

RESULTS

Morphometric analysis of lung tissues demonstrated that alveolarization was significantly inhibited only in the LPS plus hyperoxia group. IL-6 protein levels and its mRNA expression in the lungs were significantly increased only in the LPS plus hyperoxia group. Neither LPS nor hyperoxia increased IL-6 in the lungs independently. bFGF mRNA expression was significantly decreased in the LPS-treated groups. VEGF protein levels were significantly reduced by hyperoxia, whereas protein carbonyl levels were increased by intra-amniotic LPS or hyperoxia. No additional significant change to VEGF or protein carbonyl levels was produced by intra-amniotic LPS or hyperoxia. There were no significant differences in the mRNA expressions of VEGF, VEGFR-2, and TGF-beta(1).

CONCLUSIONS

The priming effect of intra-amniotic LPS on hyperoxic lung injury may be associated with IL-6 elevation in the lungs.