Enhanced expression of cytokines may play a fundamental role in the mechanisms of immunologically mediated recurrent spontaneous abortion

Acta Obstet Gynecol Scand. 1997 Mar;76(3):205-11. doi: 10.3109/00016349709048142.

Abstract

Objectives: To determine circulatory levels of IL-1 beta, TNF alpha, IFN-gamma and Neopterin in immunologically mediated recurrent abortion.

Design: Blood samples were withdrawn from both groups of first trimester recurrent abortion and controls for the determination of serum IL-1 beta, TNF alpha, IFN-gamma by the corresponding IRMA and serum neopterin by a double antibody RIA.

Setting: Department of Obstetrics & Gynecology, Cairo University Hospitals.

Patients: Thirty pregnant women in their first trimester who presented with inevitable abortion with history of at least 3 prior spontaneous consecutive abortions, in addition to twenty-three pregnant women in their first trimester presented with their first miscarriage due to chromosomal anomalies (controls). Every attempt was made to eliminate the possible known contributing factors of recurrent abortion except for the presence of cervical mucus sperm antibodies which were present in 24 out of 30 cases.

Interventions: None.

Results: Serum IL1 beta, TNF alpha and IFN-gamma levels of the abortion group were significantly elevated when compared to the corresponding levels of controls. The incidence of abnormal high values of these cytokines varied between 40 to 70%. There was no significant difference of serum neopterin between abortion and control groups. The increase of IFN gamma, the most active principle inducing neopterin release, was below the concentration needed for neopterin stimulation.

Conclusions: In view of the proven findings that cytokines do have detrimental effects on implantation, trophoblast proliferation, embryo development and fetal survival, our results suggest a potential mechanism of immunologic recurrent abortion which involves the secretion of IL-1 beta, TNF alpha, IFN gamma and other cytokines by activated endometrial lymphocytes and macrophages in response to either trophoblast or sperm antigens and these cytokines could partially defuse or penetrate into the systemic circulation.

MeSH terms

  • Abortion, Habitual / etiology*
  • Abortion, Habitual / physiopathology*
  • Adult
  • Biopterins / analogs & derivatives
  • Biopterins / blood
  • Biopterins / physiology
  • Cell Division / physiology
  • Cytokines / blood
  • Cytokines / metabolism
  • Cytokines / physiology*
  • Embryonic and Fetal Development / physiology
  • Endometrium / metabolism
  • Female
  • Humans
  • Interferon-gamma / blood
  • Interferon-gamma / physiology
  • Interleukin-1 / blood
  • Interleukin-1 / physiology
  • Neopterin
  • Pregnancy / blood
  • Pregnancy / immunology*
  • Pregnancy / physiology*
  • Trophoblasts / cytology
  • Trophoblasts / physiology
  • Tumor Necrosis Factor-alpha / analysis
  • Tumor Necrosis Factor-alpha / physiology

Substances

  • Cytokines
  • Interleukin-1
  • Tumor Necrosis Factor-alpha
  • Biopterins
  • Neopterin
  • Interferon-gamma