Preterm infants exposed to chorioamnionitis and preterm sheep fetuses exposed to intraamniotic (IA) LPS have lung inflammation, increased IL-8 levels and lung maturation. We tested the hypothesis that IL-8 signaling mediates IA LPS induced lung inflammation and lung maturation. Two strategies were used: 1) We tested if intraamniotic injection of recombinant sheep IL-8 (rsIL-8) induced fetal inflammation and 2) if IL-8 signaling was blocked by a novel CXCR2 receptor blocker, nicotinanilide thioglycolate methyl ester (NTME). To test effects of IL-8 in the fetus, rsIL-8 was given intravascularly (50microg) at 124+/-1d gestation (Term=150d). A separate group of sheep were given IA rsIL-8 (100microg) and delivered 5h to 7d later, at 124+/-1d gestation. After confirming efficacy of the CXCR2 inhibitor, effects of IL-8 blockade were tested by injecting fetal sheep intramuscularly with NTME (10mg) prior to IA injection of E.Coli LPS (10mg). Sheep fetuses were delivered 1d or 7d after injections at 124+/-1d gestation. IA rsIL-8 induced a modest 5-fold increase in broncho-alveolar lavage (BAL) monocytes and neutrophils and increased lung monocyte hydrogen peroxide generation. However, rsIL-8 did not induce lung maturation. Intravascular rsIL-8 did not change fetal cardiovascular variables, blood pH or blood leukocyte counts. Inhibition of CXCR2 decreased IA LPS induced increases in BAL proteins at 1d but not at 7d. NTME did not significantly decrease IA LPS induced BAL leukocyte influx, and lung cytokine mRNA expression. Inhibition of CXCR2 did not change IA LPS induced lung maturation. IL-8 signaling does not mediate LPS induced lung inflammation and lung maturation. Key words: Prematurity, Respiratory distress syndrome, Broncho-pulmonary dysplasia, Fetal inflammatory response syndrome.
|Pages (from-to)||L512 - L519|
|Number of pages||8|
|Journal||American Journal of Physiology - Lung Cellular and Molecular Physiology|
|Publication status||Published - 2009|
Kallapur, S. G., Moss, T. J. M., Auten Jr., R. L., Nitsos, I., Pillow, J. J., Kramer, B. W., Maeda, D. Y., Newnham, J. P., Ikegami, M., & Jobe, A. H. (2009). IL-8 signaling does not mediate intra-amniotic LPS-induced inflammation and maturation in preterm fetal lamb lung. American Journal of Physiology - Lung Cellular and Molecular Physiology, 297(3), L512 - L519. https://doi.org/10.1152/ajplung.00105.2009