Synthetic PreImplantation Factor (sPIF) reduces inflammation and prevents preterm birth

PLoS One. 2020 Jun 8;15(6):e0232493. doi: 10.1371/journal.pone.0232493. eCollection 2020.

Abstract

Preterm birth (PTB) is the leading cause of neonatal morbidity and mortality and spontaneous PTB is a major contributor. The preceding inflammation/infection contributes not only to spontaneous PTB but is associated with neonatal morbidities including impaired brain development. Therefore, control of exaggerated immune response during pregnancy is an attractive strategy. A potential candidate is synthetic PreImplantation Factor (sPIF) as sPIF prevents inflammatory induced fetal loss and has neuroprotective properties. Here, we tested maternal sPIF prophylaxis in pregnant mice subjected to a lipopolysaccharides (LPS) insult, which results in PTB. Additionally, we evaluated sPIF effects in placental and microglial cell lines. Maternal sPIF application reduced the LPS induced PTB rate significantly. Consequently, sPIF reduced microglial activation (Iba-1 positive cells) and preserved neuronal migration (Cux-2 positive cells) in fetal brains. In fetal brain lysates sPIF decreased IL-6 and INFγ concentrations. In-vitro, sPIF reduced Iba1 and TNFα expression in microglial cells and reduced the expression of pro-apoptotic (Bad and Bax) and inflammatory (IL-6 and NLRP4) genes in placental cell lines. Together, maternal sPIF prophylaxis prevents PTB in part by controlling exaggerated immune response. Given the sPIF`FDA Fast Track approval in non-pregnant subjects, we envision sPIF therapy in pregnancy.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Anti-Inflammatory Agents, Non-Steroidal / pharmacology*
  • Brain / drug effects
  • Brain / embryology
  • Brain / immunology
  • Cell Line
  • Disease Models, Animal
  • Female
  • Inflammation / immunology
  • Inflammation / therapy*
  • Lipopolysaccharides
  • Mice
  • Microglia / drug effects
  • Microglia / immunology
  • Neurons / drug effects
  • Neurons / metabolism
  • Peptides / pharmacology*
  • Pregnancy
  • Pregnancy Complications / drug therapy*
  • Pregnancy Complications / immunology
  • Premature Birth / immunology
  • Premature Birth / prevention & control*

Substances

  • Anti-Inflammatory Agents, Non-Steroidal
  • Lipopolysaccharides
  • Peptides
  • preimplantation factor, synthetic

Grants and funding

NDS and MM received an unrestricted fund from BioIncept. BioIncept provided sPIF. ERB is CSO of BioIncept. The specific roles of this authors are articulated in the ‘author contributions’ section. In addition, the following grants helped fund this research: Universita Cattolica del Sacro Cuore (D1 2015: 70201356), Instituto Scientifico Internazionale, Paolo VI Institute, Università Cattolica del Sacro Cuore, Rome, Italy to NDS, and University Hospital Bern (2019-00431) to MS and MM. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.