Loss of interleukin-6 enhances the inflammatory response associated with hyperoxia-induced lung injury in neonatal mice.

In bronchopulmonary dysplasia (BPD), decreased angiogenesis and alveolarization is associated with pulmonary cell death and inflammation. It is commonly observed in premature infants who required mechanical ventilation and oxygen therapy. Since enhanced interleukin-6 (IL-6) expression has been reported in infants with BPD, it was hypothesized that a decrease in IL-6 may enhance lung inflammation and decrease hyperoxia-induced neonatal lung injury in mice. In the current study, newborn wild-type (WT) and IL-6 null mice were treated with 85% O (hyperoxia) or 21% O (normoxia) for 96 h. Although the increased volume and decreased quantity of alveoli was triggered by hyperoxia in WT and IL-6 null mice, transcription and translation of proinflammatory cytokines (monocyte chemoattractant protein-1, IL-10, IL-12 and tumor necrosis factor-) and pulmonary cell death (caspase stimulation and terminal deoxynucleotidyl-transferase-mediated dUTP nick end labeling staining) were significantly enhanced in IL-6 null mice compared with WT mice. These results suggest that the crosstalk between inflammation and cell death may be involved in hyperoxia-induced lung injury in BPD. Future treatment approaches for bronchopulmonary dysplasia should be based on the suppression of cytokine expression.