Effect of Intralipid infusion on peripheral blood T cells and plasma cytokines in women undergoing assisted reproduction treatment.

Kerrie L Foyle,Jasmine J Wilson,David J Sharkey,Lachlan M Moldenhauer,Sarah A Robertson,Cassandra J Roccisano,Ella S Green,M Louise Hull,Kelton P Tremellen

doi:10.1002/cti2.1328

Abstract

ObjectivesIntravenous infusion of Intralipid is an adjunct therapy in assisted reproduction treatment (ART) when immune‐associated infertility is suspected. Here, we evaluated the effect of Intralipid infusion on regulatory T cells (Treg cells), effector T cells and plasma cytokines in peripheral blood of women undertaking IVF.MethodsThis prospective, observational pilot study assessed Intralipid infusion in 14 women exhibiting recurrent implantation failure, a clinical sign of immune‐associated infertility. Peripheral blood was collected immediately prior to and 7 days after intravenous administration of Intralipid. Plasma cytokines were measured by Luminex, and T‐cell subsets were analysed by flow cytometry.ResultsA small increase in conventional CD8+ T cells occurred after Intralipid infusion, but no change was seen in CD4+ Treg cells, or naïve, memory or effector memory T cells. Proliferation marker Ki67, transcription factors Tbet and RORγt, and markers of suppressive capacity CTLA4 and HLA‐DR were unchanged. Dimensionality‐reduction analysis using the tSNE algorithm confirmed no phenotype shift within Treg cells or other T cells. Intralipid infusion increased plasma CCL2, CCL3, CXCL8, GM‐CSF, G‐CSF, IL‐6, IL‐21, TNF and VEGF.ConclusionIntralipid infusion elicited elevated pro‐inflammatory cytokines, and a minor increase in CD8+ T cells, but no change in pro‐tolerogenic Treg cells. Notwithstanding the limitation of no placebo control, the results do not support Intralipid as a candidate intervention to attenuate the Treg cell response in women undergoing ART. Future placebo‐controlled studies are needed to confirm the potential efficacy and clinical significance of Intralipid in attenuating cytokine induction and circulating CD8+ T cells.

Highlights

Recurrent implantation failure occurs when overtly healthy embryos fail to implant over the course of repeated in vitro fertilisation (IVF) cycles
To explore the possibility that T cells might be responsive to Intralipid infusion in women with recurrent implantation failure, we examined T cells in peripheral blood taken from women before and after Intralipid infusion in women undertaking IVF
We found no increase in Treg cells, no substantial shift in the balance of CD4+ or CD8+ regulatory to conventional T cells, and no indication of altered phenotype in Treg cells or other T-cell subsets, which were attributable to Intralipid treatment

Summary

Introduction

Recurrent implantation failure occurs when overtly healthy embryos fail to implant over the course of repeated IVF cycles. This condition affects at least 10% of infertile women seeking in vitro fertilisation (IVF) treatment,[1] and is thought to reflect failure of the uterine endometrial lining to attain a sufficiently receptive state. Tregs are well known for their capacity to limit excessive inflammation and recalibrate tissue homeostasis after insult or injury, as well as to suppress effector T-cell reactions to self or nonself antigens.[4,5] In fetal tolerance, CD4+ Treg cells are required to suppress inflammation, prevent effector T-cell generation and support uterine vascular adaptations that underpin placental development.[4,5,6]

Objectives

Methods

Results

Discussion

Conclusion