PreImplantation Factor (PIF) orchestrates systemic antiinflammatory response by immune cells: effect on peripheral blood mononuclear cells.

Abstract

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). 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). 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). Physiologic concentrations of PIF exert potent systemic antiinflammatory effects on nonpregnant activated immune cells.