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

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 mononu...

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Published in:American journal of obstetrics and gynecology 2012-10, Vol.207 (4), p.313.e1-313.e11
Main Authors: Barnea, Eytan R., MD, Kirk, David, PhD, Ramu, Sivakumar, PhD, Rivnay, Benjamin, PhD, Roussev, Roumen, MD, PhD, Paidas, Michael J., MD
Format: Article
Language:English
Subjects:
Anti-Inflammatory Agents - pharmacology
Cell Proliferation - drug effects
Cytokines - genetics
Cytokines - metabolism
embryo
Female
Humans
immune disorder
immune modulation
Inflammation - immunology
Inflammation - metabolism
Leukocytes, Mononuclear - drug effects
Leukocytes, Mononuclear - immunology
Leukocytes, Mononuclear - metabolism
Lymphocyte Activation - drug effects
Lymphocyte Activation - immunology
Male
Obstetrics and Gynecology
Peptides - pharmacology
Pregnancy
PreImplantation Factor
RNA, Messenger - genetics
RNA, Messenger - metabolism
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Summary: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). Study Design 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). Conclusion Physiologic concentrations of PIF exert potent systemic antiinflammatory effects on nonpregnant activated immune cells.
ISSN:0002-9378
1097-6868
DOI:10.1016/j.ajog.2012.07.017