IL-8 signaling does not mediate intra-amniotic LPS-induced inflammation and maturation in preterm fetal lamb lung

S.G. Kallapur, T.J. Moss, R.L. Auten, Ilias Nitsos, Jane Pillow, B.W. Kramer, D.Y. Maeda, John Newnham, M. Ikegami, Alan Jobe

    Research output: Contribution to journalArticlepeer-review

    29 Citations (Scopus)

    Abstract

    Preterm infants exposed to chorioamnionitis and preterm sheep fetuses exposed to intra-amniotic (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 IA 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 (50 μg) at 124 ± 1 day of gestation (term = 150 days). A separate group of sheep was given IA rsIL-8 (100 μg) and delivered 5 h to 7 days later at 124 ± 1 day of gestation. After confirming efficacy of the CXCR2 inhibitor, effects of IL-8 blockade were tested by injecting fetal sheep intramuscularly with NTME (10 mg) before IA injection of Escherichia coli LPS (10 mg). Sheep fetuses were delivered 1 or 7 days after injections at 124 ± 1 day of gestation. IA rsIL-8 induced a modest fivefold increase in bronchoalveolar 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 1 day but not at 7 days. 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.
    Original languageEnglish
    Pages (from-to)L512-L519
    JournalAmerican journal of physiology : lung cellular and molecular physiology
    Volume297
    Issue number3
    DOIs
    Publication statusPublished - 2009

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