Progesterone-induced blocking factor (PIBF) modulates cytokine production by lymphocytes from women with recurrent miscarriage or preterm delivery

J Reprod Immunol. 2009 Jun;80(1-2):91-9. doi: 10.1016/j.jri.2009.01.004. Epub 2009 Apr 15.

Abstract

Spontaneous miscarriage and preterm delivery are common complications of pregnancy. Pro-inflammatory cytokines have been shown to be associated with recurrent spontaneous miscarriage (RSM) and preterm delivery (PTD) and these have led to exploration of ways to downregulate pro-inflammatory cytokines and/or to upregulate anti-inflammatory cytokines. Progesterone-induced blocking factor (PIBF) is a molecule with inhibitory effects on cell-mediated immune reactions. We have ascertained the effects of PIBF on secretion of selected type 1 and type 2 cytokines by peripheral blood mononuclear cells from healthy non-pregnant women, women undergoing normal pregnancy, women with unexplained RSM and women with PTD. Peripheral blood mononuclear cells from 30 women with a history of unexplained RSM, 18 women undergoing PTD, 11 women with normal pregnancy and 13 non-pregnant healthy women were stimulated with a mitogen in the absence and presence of PIBF after which the levels of cytokines released into culture supernatants were determined by ELISA. Production of the type 2 cytokines IL-4, IL-6 and IL-10 by lymphocytes from the RSM and PTD groups and of IL-4 and IL-10 by lymphocytes from healthy pregnant women was significantly increased upon exposure to PIBF, while the levels of type 1 cytokines were not affected. Ratios of type 1:type 2 cytokines were decreased, suggesting a shift towards Th2 bias. PIBF did not affect cytokine production by lymphocytes from non-pregnant women. Thus, PIBF acts on lymphocytes in pregnancy to induce a type 1 to type 2 cytokine shift by upregulating the production of type 2 cytokines.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Abortion, Habitual / blood
  • Abortion, Habitual / immunology*
  • Abortion, Habitual / pathology
  • Cells, Cultured
  • Cytokines / metabolism*
  • Enzyme-Linked Immunosorbent Assay
  • Female
  • Humans
  • Immune Tolerance
  • Lymphocyte Activation
  • Placenta / immunology*
  • Placenta / pathology
  • Pregnancy
  • Pregnancy Proteins / immunology
  • Pregnancy Proteins / metabolism*
  • Premature Birth / blood
  • Premature Birth / immunology*
  • Premature Birth / pathology
  • Suppressor Factors, Immunologic / immunology
  • Suppressor Factors, Immunologic / metabolism*
  • Th1 Cells / immunology
  • Th1 Cells / metabolism
  • Th1 Cells / pathology
  • Th2 Cells / immunology
  • Th2 Cells / metabolism
  • Th2 Cells / pathology

Substances

  • Cytokines
  • PIBF1 protein, human
  • Pregnancy Proteins
  • Suppressor Factors, Immunologic