Temporal Association Between Pulmonary Inflammation and Antioxidant Induction Following Hyperoxic Exposure of the Preterm Guinea Pig

Abstract

The time course and nature of the pulmonary inflammatory and antioxidant responses, both during and after hyperoxic-induced acute lung injury were studied in the preterm guinea pig. Three-day preterm (65 days gestation) guinea pigs were randomly exposed to either 21% O₂ (control) or 95% O₂ (hyperoxia) for 72 hours. All pups were then maintained in ambient conditions for up to a further 11 days, during which time lung damage was monitored. In animals exposed to hyperoxia, evidence of acute lung injury and inflammation was characterized by a marked increase in microvascular permeability and elevated numbers of neutrophils in bronchoalveolar lavage fluid. Protein concentration, elastase-like activity and elastase-inhibitory capacity in lavage fluid were at a maximum at the end of the 72 hours hyperoxic exposure. Four days later, all values had returned to control levels. In contrast, increased numbers of neutrophils, macrophages and lymphocytes were recovered in the lavage fluid during this early recovery period. Coinciding with the influx of inflammatory cells, there was a significant increase in glutathione peroxidase, manganese superoxide dismutase and catalase activities in immature lung. Lung copper/zinc superoxide dismutase activity remained unchanged during both experimental periods. The strong temporal relationship between the influx of inflammatory cells to the lung and the induction of pulmonary antioxidant enzyme defences suggests that a common mechanism underlies both responses. These findings have led us to regard inflammation in the hyperoxic-injured immature lung as a beneficial event and not, as previously suggested, as part of the injurious process.

Key Words:

• Pulmonary oedema
• superoxide dismutase
• glutathione peroxidase
• catalase
• interleukin 1
• tumour necrosis factor
• elastase activity.
• BAL bronchoalveolar lavage
• CAT catalase
• CLD chronic lung disease
• Cu/Zn-SOD copper/zinc superoxide dismutase
• EDTA ethylenediaminetetra-acetate
• EIC elastase inhibitory capacity
• ELA elastase-like activity
• GSH-Px glutathione peroxidase
• IL-1 interleukin 1
• Mn-SOD manganese superoxide dismutase
• O₂ oxygen
• PMSF phenylmethylesulphonyl fluoride
• PPE porcine pancreatic elastase
• RDS respiratory distress syndrome
• SLAPN succinyl-1-trianyl-p-nitroanilide
• TNF tumour necrosis factor