Background: There is little knowledge on the immune system of extremely premature infants. This paucity of evidence impedes advances in the fight against bronchopulmonary dysplasia (BPD), a common, severe chronic lung disease that entails significant morbidity and mortality. No safe and effective treatment exists.

Method:  Blood was collected from extremely preterm infants at 5 timepoints [birth, days 1, 7 and 14 and 36 weeks corrected gestational age (WCGA)]. Following overnight stimulation with PMA/ionomycin, LPS or vehicle in whole blood assays, flow cytometry was used to explore T cells and their polarisation, macrophages and dendritic cells (DC) and their activation status and endothelial progenitor cells (EPC).

Results: In preterm babies, expression of the activation marker MHC II progressively increased over time on macrophages (d1, 48% vs 36-WCGA, 86%) and DC (d1, 24% vs 36-WCGA, 56%). Comparing the one infant that developed BPD with the two that did not at 36-WCGA, we observed a marked increase in macrophage (6-fold) and DC activation (2-fold), but fewer circulating EPC (0.3% vs 1.4% of viable cells). Unexpectedly, we also found that preterm infants are capable of producing the cytokines IFN-gamma and IL-17A.

Conclusions: It only took the results from three preterm infants to reveal that this first-of-its-kind study will revolutionise the understanding of preterm immunity; for example, these data suggest that, contrary to current belief, preterm babies are capable of producing IFN-gamma and IL-17. BPD appears associated with markedly increased cellular activation - a promising finding that may provide a basis for therapeutic innovations.