TEMPORAL ASSOCIATION BETWEEN PULMONARY INFLAMMATION AND ANTIOXIDANT INDUCTION FOLLOWING HYPEROXIC EXPOSURE OF THE PRETERM GUINEA-PIG

The time course and nature of the pulmonary inflammatory and antioxida nt responses, both during and after hyperoxic-induced acute lung injur y were studied in the preterm guinea pig. Three-day preterm (65 days g estation) 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 ac ute lung injury and inflammation was characterized by a marked increas e in microvascular permeability and elevated numbers of neutrophils in bronchoalveolar lavage fluid. Protein concentration, elastase-like ac tivity and elastase-inhibitory capacity in lavage fluid were at a maxi mum at the end of the 72 hours hyperoxic exposure. Four days later, al l values had returned to control levels. In contrast, increased number s of neutrophils, macrophages and lymphocytes were recovered in the la vage fluid during this early recovery period. Coinciding with the infl ux of inflammatory cells, there was a significant increase in glutathi one peroxidase, manganese superoxide dismutase and catalase activities in immature lung. Lung copper/zinc superoxide dismutase activity rema ined unchanged during both experimental periods. The strong temporal r elationship between the influx of inflammatory cells to the lung and t he 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 ben eficial event and not, as previously suggested, as part of the injurio us process.