Premature very low birth weight infants are at an increased risk for developing bronchopulmonary dysplasia (BPD), a chronic lung disease resulting from pulmonary inflammation and subsequent fibrosis of lung tissue. While the exact immunoregulatory mechanisms that underlie BPD are poorly understood, the infiltration of PMNs into the lung in response to the chemokines IL-8 and ENA-78 is essential to the development of BPD. Furthermore, evidence might suggest that nutritional deficiencies contribute to the incidence of BPD observed in premature newborns.

These studies were designed to determine if retinoic acid (RA) regulates the production of inflammatory cytokines by alveolar type II epithelial cells. Using a cytokine-specific ELISA, we measured the effect of RA on the levels of IL-8 and ENA-78 produced by type II epithelial cells (A549) in response to the pro-inflammatory cytokines IL-1 and TNF-α. Also, we utilized RT-PCR to examine the effect of RA on the mRNAs for IL-8 and ENA-78 in these cultures. The results of these studies demonstrate that RA, in a dose-dependent fashion, inhibits the production of IL-8 and ENA-78 by A549 cells following stimulation of these cells with macrophage-derived pro-inflammatory cytokines. The RT-PCR analysis suggests that RA inhibits the production of each of these two cytokines by different mechanisms. These studies also provide a molecular basis for a role of RA deficiency in the development of BPD.