title: PreImplantation Factor (PIF) orchestrates systemic antiinflammatory response by immune cells: effect on peripheral blood mononuclear cells.
abstract: OBJECTIVE
  Embryo-derived PreImplantation Factor (PIF) is essential for pregnancy immune modulation and synthetic PIF (sPIF), reverses neuroinflammation, and prevents diabetes mellitus through its immune modulatory properties. Herein, we explore sPIF's systemic effects on peripheral blood mononuclear cells (PBMCs).
  
  
  METHODS
  sPIF's effects on PBMCs and subset populations from nonpregnant patients (n = 7) and male patients were evaluated by the assessment of binding characteristics, mixed lymphocyte reaction, proliferation, cytokine secretion, and associated gene expression. Data analysis was by analysis of variance (P < .05).
  
  
  RESULTS
  Fluorescein isothiocyanate-sPIF bound all myelomonocytic cells; binding was 30-fold up-regulated in mitogen-activated T and B cells (P < .05). sPIF decreased mixed lymphocyte reaction by 70% and blocked anti-CD3 antibody stimulated-PBMC proliferation by approximately 80% (P < .05). In naïve PBMCs, sPIF reduced interleukin (IL)-10 and -2; in activated PBMCs, sPIF increased IL-4, -5, -10, and -2, tumor necrosis factor-α, interferon-γ, and granulocyte-macrophage colony-stimulating factor (P < .05).
  
  
  CONCLUSIONS
  Physiologic concentrations of PIF exert potent systemic antiinflammatory effects on nonpregnant activated immune cells.
authors.affiliation: Society for the Investigation of Early Pregnancy and BioIncept, LLC, Cherry Hill, NJ, USA. barnea@earlypregnancy.org
authors.forename: Eytan R
authors.initials: ER
authors.lastname: Barnea
authors.forename: David
authors.initials: D
authors.lastname: Kirk
authors.forename: Sivakumar
authors.initials: S
authors.lastname: Ramu
authors.forename: Benjamin
authors.initials: B
authors.lastname: Rivnay
authors.forename: Roumen
authors.initials: R
authors.lastname: Roussev
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Paidas
mesh_terms: D000893:Anti-Inflammatory Agents / Q000494:pharmacology*; D049109:Cell Proliferation / Q000187:drug effects*; D016207:Cytokines / Q000235:genetics / Q000378:metabolism*; D005260:Female; D006801:Humans; D007249:Inflammation / Q000276:immunology / Q000378:metabolism; D007963:Leukocytes, Mononuclear / Q000187:drug effects / Q000276:immunology* / Q000378:metabolism; D008213:Lymphocyte Activation / Q000187:drug effects* / Q000276:immunology; D008297:Male; D010455:Peptides / Q000494:pharmacology*; D011247:Pregnancy; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism
chemical_list: D000893:Anti-Inflammatory Agents; D016207:Cytokines; D010455:Peptides; D012333:RNA, Messenger; C569738:preimplantation factor, synthetic