188: Absence of IL-6 does not decrease pulmonary inflammation in two models of bronchopulmonary dysplasia (BPD)

Abstract

BPD is the result of chronic pulmonary inflammation and abnormal alveolar remodeling. IL-6 is an inflammatory mediator which has been implicated in this process. Two models which produce BPD in mice have been previously reported. We sought to determine if perinatal IL-6 absence in these models of BPD attenuated pulmonary inflammation. IL-6 knockout (-/-) mice were compared wild-type C57BI6J mice (+/+) in order to determine if this exposure improved pulmonary inflammation. Day 14 Antepartum lipopolysaccharide (LPS) with and without postpartum hyperoxia were the two models of BPD. Litters were homogenized at birth and then randomly assigned by model type. On day 14 of life pups were sacrificed, and one third of them were randomly selected for assessment of inflammation. The primary outcome was pulmonary inflammation measured by inflammasome caspase-1 fluorometric activity at 14 days of life. Relative fluorescence units (RFU) were controlled by total protein concentration of each sample. Unpaired t-tests were utilized to determine differences between mice type for each model of BPD; a p-value < 0.05 was considered statistically significant. 23 pups were randomly selected for molecular inflammation analysis. In the LPS only model, 8 pups were analyzed. In the LPS and hyperoxia model, 15 pups were analyzed. There was no significant decrease in pulmonary inflammation between -/- and +/+ in the LPS only group (1213 vs 920 RFU/total protein, p=0.38). Additionally, there was no difference in pulmonary inflammation between the -/- and +/+ mice in the LPS and hyperoxia group (1650 vs 1559 RFU/total protein, p=0.76). Genetic IL-6 absence did not decrease pulmonary inflammation in two mouse models of BPD. Future studies should examine if a more physiologic imperfect IL-6 blockade will decrease pulmonary inflammation, due to IL-6’s roles in both the resolution of innate immunity and the development of acquired immunity.