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Inflammation-Induced Adverse Pregnancy and Neonatal Outcomes Can Be Improved by the Immunomodulatory Peptide Exendin-4
Preterm birth is the leading cause of neonatal morbidity and mortality worldwide. Inflammation is causally linked to preterm birth; therefore, finding an intervention that dampens maternal and fetal inflammatory responses may provide a new strategy to prevent adverse pregnancy and neonatal outcomes....
Autores principales: | , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Frontiers Media S.A.
2018
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6015905/ https://www.ncbi.nlm.nih.gov/pubmed/29967606 http://dx.doi.org/10.3389/fimmu.2018.01291 |
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author | Garcia-Flores, Valeria Romero, Roberto Miller, Derek Xu, Yi Done, Bogdan Veerapaneni, Chharitha Leng, Yaozhu Arenas-Hernandez, Marcia Khan, Nabila Panaitescu, Bogdan Hassan, Sonia S. Alvarez-Salas, Luis Marat Gomez-Lopez, Nardhy |
author_facet | Garcia-Flores, Valeria Romero, Roberto Miller, Derek Xu, Yi Done, Bogdan Veerapaneni, Chharitha Leng, Yaozhu Arenas-Hernandez, Marcia Khan, Nabila Panaitescu, Bogdan Hassan, Sonia S. Alvarez-Salas, Luis Marat Gomez-Lopez, Nardhy |
author_sort | Garcia-Flores, Valeria |
collection | PubMed |
description | Preterm birth is the leading cause of neonatal morbidity and mortality worldwide. Inflammation is causally linked to preterm birth; therefore, finding an intervention that dampens maternal and fetal inflammatory responses may provide a new strategy to prevent adverse pregnancy and neonatal outcomes. Using animal models of systemic maternal inflammation [intraperitoneal injection of lipopolysaccharide (LPS)] and fetal inflammation (intra-amniotic administration of LPS), we found that (1) systemic inflammation induced adverse pregnancy and neonatal outcomes by causing a severe maternal cytokine storm and a mild fetal cytokine response; (2) fetal inflammation induced adverse pregnancy and neonatal outcomes by causing a mild maternal cytokine response and a severe fetal cytokine storm; (3) exendin-4 (Ex4) treatment of dams with systemic inflammation or fetal inflammation improved adverse pregnancy outcomes by modestly reducing the rate of preterm birth; (4) Ex4 treatment of dams with systemic, but not local, inflammation considerably improved neonatal outcomes, and such neonates continued to thrive; (5) systemic inflammation facilitated the diffusion of Ex4 through the uterus and the maternal–fetal interface; (6) neonates born to Ex4-treated dams with systemic inflammation displayed a similar cytokine profile to healthy control neonates; and (7) treatment with Ex4 had immunomodulatory effects by inducing an M2 macrophage polarization and increasing anti-inflammatory neutrophils, as well as suppressing the expansion of CD8+ regulatory T cells, in neonates born to dams with systemic inflammation. Collectively, these results provide evidence that dampening maternal systemic inflammation through novel interventions, such as Ex4, can improve the quality of life for neonates born to women with this clinical condition. |
format | Online Article Text |
id | pubmed-6015905 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2018 |
publisher | Frontiers Media S.A. |
record_format | MEDLINE/PubMed |
spelling | pubmed-60159052018-07-02 Inflammation-Induced Adverse Pregnancy and Neonatal Outcomes Can Be Improved by the Immunomodulatory Peptide Exendin-4 Garcia-Flores, Valeria Romero, Roberto Miller, Derek Xu, Yi Done, Bogdan Veerapaneni, Chharitha Leng, Yaozhu Arenas-Hernandez, Marcia Khan, Nabila Panaitescu, Bogdan Hassan, Sonia S. Alvarez-Salas, Luis Marat Gomez-Lopez, Nardhy Front Immunol Immunology Preterm birth is the leading cause of neonatal morbidity and mortality worldwide. Inflammation is causally linked to preterm birth; therefore, finding an intervention that dampens maternal and fetal inflammatory responses may provide a new strategy to prevent adverse pregnancy and neonatal outcomes. Using animal models of systemic maternal inflammation [intraperitoneal injection of lipopolysaccharide (LPS)] and fetal inflammation (intra-amniotic administration of LPS), we found that (1) systemic inflammation induced adverse pregnancy and neonatal outcomes by causing a severe maternal cytokine storm and a mild fetal cytokine response; (2) fetal inflammation induced adverse pregnancy and neonatal outcomes by causing a mild maternal cytokine response and a severe fetal cytokine storm; (3) exendin-4 (Ex4) treatment of dams with systemic inflammation or fetal inflammation improved adverse pregnancy outcomes by modestly reducing the rate of preterm birth; (4) Ex4 treatment of dams with systemic, but not local, inflammation considerably improved neonatal outcomes, and such neonates continued to thrive; (5) systemic inflammation facilitated the diffusion of Ex4 through the uterus and the maternal–fetal interface; (6) neonates born to Ex4-treated dams with systemic inflammation displayed a similar cytokine profile to healthy control neonates; and (7) treatment with Ex4 had immunomodulatory effects by inducing an M2 macrophage polarization and increasing anti-inflammatory neutrophils, as well as suppressing the expansion of CD8+ regulatory T cells, in neonates born to dams with systemic inflammation. Collectively, these results provide evidence that dampening maternal systemic inflammation through novel interventions, such as Ex4, can improve the quality of life for neonates born to women with this clinical condition. Frontiers Media S.A. 2018-06-18 /pmc/articles/PMC6015905/ /pubmed/29967606 http://dx.doi.org/10.3389/fimmu.2018.01291 Text en Copyright © 2018 Garcia-Flores, Romero, Miller, Xu, Done, Veerapaneni, Leng, Arenas-Hernandez, Khan, Panaitescu, Hassan, Alvarez-Salas and Gomez-Lopez. https://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms. |
spellingShingle | Immunology Garcia-Flores, Valeria Romero, Roberto Miller, Derek Xu, Yi Done, Bogdan Veerapaneni, Chharitha Leng, Yaozhu Arenas-Hernandez, Marcia Khan, Nabila Panaitescu, Bogdan Hassan, Sonia S. Alvarez-Salas, Luis Marat Gomez-Lopez, Nardhy Inflammation-Induced Adverse Pregnancy and Neonatal Outcomes Can Be Improved by the Immunomodulatory Peptide Exendin-4 |
title | Inflammation-Induced Adverse Pregnancy and Neonatal Outcomes Can Be Improved by the Immunomodulatory Peptide Exendin-4 |
title_full | Inflammation-Induced Adverse Pregnancy and Neonatal Outcomes Can Be Improved by the Immunomodulatory Peptide Exendin-4 |
title_fullStr | Inflammation-Induced Adverse Pregnancy and Neonatal Outcomes Can Be Improved by the Immunomodulatory Peptide Exendin-4 |
title_full_unstemmed | Inflammation-Induced Adverse Pregnancy and Neonatal Outcomes Can Be Improved by the Immunomodulatory Peptide Exendin-4 |
title_short | Inflammation-Induced Adverse Pregnancy and Neonatal Outcomes Can Be Improved by the Immunomodulatory Peptide Exendin-4 |
title_sort | inflammation-induced adverse pregnancy and neonatal outcomes can be improved by the immunomodulatory peptide exendin-4 |
topic | Immunology |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6015905/ https://www.ncbi.nlm.nih.gov/pubmed/29967606 http://dx.doi.org/10.3389/fimmu.2018.01291 |
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