Lack of in vitro effect of aglepristone on IFN-γ and IL-4 production by resting and mitogen-activated T cells of luteal bitches

Piotr Jurka,Anna Winnicka,Lidia Szulc-Dąbrowska,Joanna Borkowska

doi:10.1186/1746-6148-9-220

Abstract

BackgroundAglepristone (RU534) is an antiprogestin used for pregnancy termination, parturition induction and conservative pyometra treatment in bitches. Its molecular structure is similar to mifepristone, an antiprogestin used in human medicine. Mifepristone has been shown to suppress proliferation and cytokine production by T cells, whereas the effect of aglepristone on T cell function remains elusive. The purpose of this project was to investigate the in vitro influence of RU534 on IFN-γ and IL-4 synthesis by peripheral blood T cells isolated from healthy bitches (N = 16) in luteal phase. The peripheral blood mononuclear cells (PBMCs) were incubated with three different dosages of aglepristone, or dimethyl sulfoxide (DMSO), with or without mitogen. The production of cytokines by resting or mitogen-activated T cells was determined by intercellular staining and flow cytometry analysis or ELISA assay, respectively.ResultsOur results showed no statistically significant differences in the percentage of IFN-γ and IL-4-synthesizing CD4+ or CD8+ resting T cells between untreated and aglepristone-treated cells at 24 and 48 hours post treatment. Moreover, mitogen-activated PBMCs treated with RU534 displayed similar concentration of IFN-γ and IL-4 in culture supernatants to those observed in mitogen-activated DMSO-treated PBMCs. Presented results indicate that administration of aglepristone for 48 hours has no influence on IFN-γ and IL-4 synthesis by resting and mitogen-activated T cells isolated from diestral bitches.ConclusionsWe conclude that antiprogestins may differentially affect T cell function depending on the animal species in which they are applied.

Highlights

Aglepristone (RU534) is an antiprogestin used for pregnancy termination, parturition induction and conservative pyometra treatment in bitches
Synthesis of IFN-γ and IL-4 by CD4+ and CD8+ T cellstreated with aglepristone We examined the in vitro effect of aglepristone on the synthesis of IFN-γ and IL-4 by canine CD4+ and CD8+ T cells isolated from peripheral blood of bitches in the luteal phase
The percentage of cytokine-producing T cells and mean fluorescent intensity (MFI) of cytokine-positive T cells treated with aglepristone were normalized to the dimethyl sulfoxide (DMSO)-treated control cells

Summary

Introduction

Aglepristone (RU534) is an antiprogestin used for pregnancy termination, parturition induction and conservative pyometra treatment in bitches. Mifepristone has been shown to suppress proliferation and cytokine production by T cells, whereas the effect of aglepristone on T cell function remains elusive. The purpose of this project was to investigate the in vitro influence of RU534 on IFN-γ and IL-4 synthesis by peripheral blood T cells isolated from healthy bitches (N = 16) in luteal phase. Aglepristone (RU534) is the only registered antiprogestin in veterinary medicine This nuclear progesterone receptor (nPR) antagonist has a higher affinity for nPR than progesterone itself [1]. The administration of aglepristone during the early luteal phase in healthy non-pregnant bitches shortened the interestrous interval suggesting that aglepristone influences the hypothalamic-pituitary-ovarian axis [7]

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