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Inflammation-Induced Adverse Pregnancy and Neonatal Outcomes Can Be Improved by the Immunomodulatory Peptide

Valeria Garcia-Flores1,2,3,4, Roberto Romero1,2,5,6,7, Derek Miller1,2,3,8

  • 1Perinatology Research Branch, Program for Perinatal Research and Obstetrics, Division of Intramural Research, Eunice Kennedy Shriver National Institute of Child Health and Human Development, NICHD/NIH/DHHS, Detroit, MI, United States.

Frontiers in Immunology
|July 4, 2018
PubMed

Insights

Exendin-4 (Ex4) treatment reduced preterm birth rates and improved neonatal outcomes in animal models by dampening maternal inflammation. This intervention shows promise for preventing adverse pregnancy and neonatal outcomes linked to inflammation.

Area of Science:

  • Reproductive Biology
  • Immunology
  • Neonatal Medicine

Background:

  • Preterm birth is a major global cause of infant illness and death.
  • Inflammation is a known cause of preterm birth, necessitating interventions to reduce maternal and fetal inflammatory responses.
  • Targeting inflammatory pathways may offer a novel strategy to prevent adverse pregnancy and neonatal outcomes.

Purpose of the Study:

  • To investigate the effects of exendin-4 (Ex4) on maternal and fetal inflammatory responses and pregnancy outcomes in animal models.
  • To determine if Ex4 can mitigate adverse outcomes associated with systemic maternal inflammation and fetal inflammation.
  • To explore the immunomodulatory mechanisms of Ex4 in neonates exposed to maternal inflammation.

Main Methods:

  • Animal models were used to simulate systemic maternal inflammation (lipopolysaccharide injection) and fetal inflammation (intra-amniotic LPS).
  • Exendin-4 (Ex4) was administered to dams experiencing inflammation.
  • Pregnancy outcomes, neonatal outcomes, cytokine profiles, and immune cell populations (macrophages, neutrophils, T cells) were analyzed.

Main Results:

  • Systemic maternal inflammation caused severe maternal and mild fetal cytokine responses, while fetal inflammation caused mild maternal and severe fetal cytokine responses, both leading to adverse outcomes.
  • Ex4 treatment modestly reduced preterm birth rates in both systemic and fetal inflammation models.
  • Ex4 significantly improved neonatal outcomes in the systemic inflammation model, normalizing neonatal cytokine profiles and inducing beneficial immunomodulatory effects, including M2 macrophage polarization and increased anti-inflammatory neutrophils.

Conclusions:

  • Dampening maternal systemic inflammation with Ex4 can improve pregnancy and neonatal outcomes.
  • Ex4 demonstrates immunomodulatory effects, suggesting its potential as a therapeutic agent for preventing preterm birth and improving neonatal health in cases of maternal inflammation.
  • Targeting maternal inflammation via interventions like Ex4 offers a promising strategy to enhance neonatal survival and well-being.

Keywords:
M2 macrophagesamniotic fluidclinical chorioamnionitisfetal inflammatory response syndromeintra-amniotic infection/inflammationneutrophilspreterm labor and birthregulatory T cells

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