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This Article Full Text Full Text (PDF) All Versions of this Article: 297/3/L512    most recent 00105.2009v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in Web of Science Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Google Scholar Articles by Kallapur, S. G. Articles by Jobe, A. H. PubMed PubMed Citation Articles by Kallapur, S. G. Articles by Jobe, A. H.

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

¹Cincinnati Children's Hospital Medical Center, University of Cincinnati, Division of Pulmonary Biology, Cincinnati, Ohio; ²Department of Physiology, Monash University, Clayton, Victoria, Australia; ³Department of Pediatrics, Duke University School of Medicine, Durham, North Carolina; ⁴School of Women's and Infants' Health, University of Western Australia, Perth, Australia; ⁵Department of Pediatrics, Maastricht University Medical Center, Maastricht, The Netherlands; and ⁶Syntrix Biosystems, Auburn, Washington

Submitted 31 March 2009 ; accepted in final form 1 July 2009

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.

prematurity; respiratory distress syndrome; bronchopulmonary dysplasia; fetal inflammatory response syndrome; CXCR2