Effect of nitric oxide and TH1/TH2 cytokine supplementation over ectopic endometrial tissue growth in a murine model of endometriosis

Reprod Sci. 2013 Nov;20(11):1332-8. doi: 10.1177/1933719113485297. Epub 2013 Apr 18.

Abstract

Using a murine model, we evaluated the growth of ectopic endometrial tissue in the presence of T helper 1 (Th1) or Th2 cytokines or a nitric oxide donor (S-nitroso-N-acetyl-penicillamine [SNAP]). Female mice were autografted with endometrial tissue in the peritoneum. Different combinations and concentrations of cytokines or SNAP were injected intraperitoneally for 8 weeks. Implants were recovered, measured, and weighed. Cytokines were determined in plasma. Implants (weight and area) were smaller in mice that received interferon γ plus interleukin 2 (IFN-γ + IL-2) compared to mice treated with IL-2, IL-4 + IL-10 or saline solution, and saline solution compared to different concentrations of SNAP. The IL-2, IFN-γ, and IL-4 concentrations in plasma decreased in accordance with the increase in SNAP concentrations compared to saline solution. The promotion of a Th1 milieu in the peritoneum reduced the weight and area of the implant. Different concentrations of SNAP suppressed Th1 and Th2 cytokines and enabled the growth of the implant in this murine model.

Keywords: IFN-γ; IL-2; SNAP; autografted endometrium; immune response.

MeSH terms

  • Animals
  • Cell Proliferation / drug effects*
  • Cytokines / administration & dosage
  • Cytokines / blood
  • Cytokines / pharmacology*
  • Disease Models, Animal
  • Dose-Response Relationship, Drug
  • Endometrium / drug effects*
  • Endometrium / immunology
  • Endometrium / metabolism
  • Endometrium / pathology
  • Endometrium / transplantation
  • Female
  • Injections, Intraperitoneal
  • Interferon-gamma / pharmacology
  • Interleukin-2 / pharmacology
  • Interleukin-4 / pharmacology
  • Mice
  • Mice, Inbred BALB C
  • Nitric Oxide / metabolism*
  • Nitric Oxide Donors / administration & dosage
  • Nitric Oxide Donors / metabolism
  • Nitric Oxide Donors / pharmacology*
  • S-Nitroso-N-Acetylpenicillamine / administration & dosage
  • S-Nitroso-N-Acetylpenicillamine / metabolism
  • S-Nitroso-N-Acetylpenicillamine / pharmacology*
  • Th1 Cells / drug effects*
  • Th1 Cells / immunology
  • Th1 Cells / metabolism
  • Th2 Cells / drug effects*
  • Th2 Cells / immunology
  • Th2 Cells / metabolism
  • Time Factors

Substances

  • Cytokines
  • Interleukin-2
  • Nitric Oxide Donors
  • Interleukin-4
  • Nitric Oxide
  • S-Nitroso-N-Acetylpenicillamine
  • Interferon-gamma