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Chronic Hypoxemia Absent Bacterial Infection Is One Cause of the Fetal Inflammatory Response Syndrome (FIRS)

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Abstract

The object of the investigation was to determine whether chronic fetal hypoxemia triggers a systemic fetal inflammatory response absent bacterial infection. Chronically hypoxemic (10.5% O2) and lipopolysac-charide (LPS; 400 µg/kg of maternal body weight) injected intrauterine (but extra-amniotic) treated pregnant guinea pigs were used with appropriate controls. The presence of bacteria in the amniotic cavity was sought using polymerase chain reaction (PCR). Interleukin 6 (IL–6) and tumor necrosis factor α (TNF-α) protein levels were measured in fetal sera and amniotic fluid (AF) by a commercially available, sensitive enzyme-linked immunosorbent assay (ELISA; IL–6 and TNF-α messenger RNA (mRNA) were also quantified in multiple fetal organs using real-time PCR. Prokaryotic DNA was not amplified from any sample, confirming the animals were not infected. Chronic hypoxemia dramatically increased IL–6 and TNF-α proteins in fetal sera and mRNA in lung, heart, and brain. There were no significant changes in either cytokine observed in the AF, fetal membranes, or fetal liver. Intrauterine but extra amniotic LPS also increased IL–6 and TNF-α protein in fetal sera and mRNA in lung, heart, and brain, plus increased the levels of both cytokines (protein/mRNA) in AF, fetal membranes, and fetal liver. Thus, an elevation in fetal blood IL–6 is not a specific marker of infection-induced fetal inflammatory response syndrome (FIRS). And in contrast to the fetal blood, an elevation in AF IL–6 seems associated only with LPS-induced FIRS.

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Authors and Affiliations

  1. Department of Obstetrics and Gynecology, Institute for Maternal Fetal Biology, Center for Reproductive Studies, and Department of Molecular and Integrative Physiology, University of Kansas School of Medicine, 3901 Rainbow Blvd, MS2028, 66160, KS, Kansas City, USA

    Yafeng Dong PhD, Weijian Hou PhD, Jiaxue Wei MD & Carl P. Weiner MD, MBA

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  1. Yafeng Dong PhD
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  2. Weijian Hou PhD
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  3. Jiaxue Wei MD
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  4. Carl P. Weiner MD, MBA
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Correspondence to Carl P. Weiner MD, MBA.

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Dong, Y., Hou, W., Wei, J. et al. Chronic Hypoxemia Absent Bacterial Infection Is One Cause of the Fetal Inflammatory Response Syndrome (FIRS). Reprod. Sci. 16, 650–656 (2009). https://doi.org/10.1177/1933719109333662

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