Gonadotropin-releasing hormone analogues lead to pro-inflammatory changes in T lymphocytes

Am J Reprod Immunol. 2016 Jul;76(1):50-8. doi: 10.1111/aji.12522.

Abstract

Problem: We aimed to investigate the effect of gonadotropin-releasing hormone (GnRH) analogues on T-cell immunity.

Method of study: TNF-α(+) -, INF-ɣ(+) -, IL-10(+) -, and IL-17(+) -expressing T cells in peripheral blood mononuclear cells (PBMCs) were treated with various concentrations (0.1, 1, 5, and 10 μm) of GnRH agonist (buserelin acetate) and antagonist (cetrorelix acetate) for 4 hours in vitro and they were analyzed with flow cytometry.

Results: TNF-α(+) /IL-10(+) T helper (TH) cell ratios were increased in PBMCs treated with 1, 5, and 10 μm GnRH agonist when compared to controls (P=.006, P=.014 and P=.030, respectively). IFN-ɣ(+) /IL-10(+) TH cell ratios were significantly increased with 0.1, 1, 5, and 10 μm GnRH agonist as compared with controls (P=.046, P=.004, P=.013, and P=.011, respectively). TNF-α(+) TH cell levels, and IFN-γ(+) /IL-10(+) TH cell ratios were significantly different (P<.001 and P<.004, respectively) between GnRH agonist- and antagonist-treated cells.

Conclusion: GnRH analogues induce pro-inflammatory TH1 shift in T-cell immunity, in vitro. GnRH treatment during assisted reproductive technology cycle might explain a possible cause of inflammatory flare in women with inflammatory conditions.

Keywords: GnRH agonist; GnRH antagonist; T helper (TH) 1 immunity; TH17; gonadotropin-releasing hormone (GnRH).

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Buserelin / pharmacology*
  • Cytokines / immunology*
  • Female
  • Gonadotropin-Releasing Hormone / agonists
  • Gonadotropin-Releasing Hormone / analogs & derivatives*
  • Gonadotropin-Releasing Hormone / antagonists & inhibitors
  • Gonadotropin-Releasing Hormone / pharmacology
  • Humans
  • Immunity, Cellular / drug effects*
  • Inflammation / drug therapy
  • Inflammation / immunology
  • Inflammation / pathology
  • Middle Aged
  • Th1 Cells / immunology*
  • Th1 Cells / pathology

Substances

  • Cytokines
  • Gonadotropin-Releasing Hormone
  • cetrorelix
  • Buserelin