Prednisone may induce immunologic tolerance by activating the functions of decidual immune cells in early pregnancy

Fu, Xiaoqian; Cai, Jun-Ying; Huang, Qiangru; Li, Dong-Ju; Li, Ning; Li, Mujun

doi:10.18632/oncotarget.22188

Cited by 9 publications

(6 citation statements)

References 27 publications

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“…12 Previous studies have observed a counterbalanced lymphocyte distribution in uRPL patients treated with PRS; thus, the treatment re-established the immune system presumed to be beneficial for embryo implantation. [21][22][23][24] The same effects have been observed in uRPL patients treated with IVIg. 22 25-27 For that reason, treatment before pregnancy with PRS and IVIg (PRS&IVIg) is expected to contribute to a favourable immunological environment in peripheral blood and the uterus which is expected to increase the chance of an uncomplicated pregnancy.…”

Section: Strengths and Limitations Of This Studysupporting

confidence: 67%

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Intravenous immunoglobulin and prednisolone to women with unexplained recurrent pregnancy loss after assisted reproductive technology treatment: a protocol for a randomised, double-blind, placebo-controlled trial

et al. 2022

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IntroductionRecurrent pregnancy loss (RPL), defined as two or more consecutive pregnancy losses in the first trimester, affects around 5% of fertile women. The underlying causes remain unknown in up to 60% of patients; however, most studies point at an immunological pathology in unexplained RPL, and therefore, an effective treatment may be immunomodulatory. This study aims to evaluate the effect of intravenous immunoglobulin (IVIg) and prednisolone on reproductive outcome and the immune system in women with unexplained RPL undergoing assisted reproductive technology treatment.Methods and analysisThis randomised, placebo-controlled trial with double-blinded randomisation to two parallel arms evaluate if immunomodulatory (active) treatment is superior to placebo in increasing the chance of ongoing pregnancy assessed at nuchal translucency scan in gestational weeks (GW) 11–13 after embryo transfer (ET) in 74 RPL patients with ≥2 pregnancy losses as its primary objective. The active treatment consists of IVIg (one infusion preferably 1–5 days before ET and in GW 5, 6 and 7) and prednisolone (5 mg/day from first day of menstrual bleeding until ET and 10 mg/day from ET to GW 8+0) while the comparator consists of intravenous human albumin (5%) and placebo tablets. Allocation is concealed for participants, caregivers, and investigators until trial termination and is performed in a 1:1 ratio. The secondary objective is to evaluate treatment safety, and the tertiary objective is exploration of the association between treatment, reproductive outcome after ET, and the lymphocyte subset distribution in peripheral blood collected before and after intravenous infusion(s). Excess biological material is stored in a biobank for future research.Ethics and disseminationThe North Denmark Region Committee on Health Research Ethics (N-20200066) approved this trial. The results will be published in peer-reviewed scientific journals and presented to relevant patient associations, at relevant academic conferences and to key stakeholders.Trial registration numberNCT04701034.

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Section: Strengths and Limitations Of This Studysupporting

confidence: 67%

“…Previous studies have observed a counterbalanced lymphocyte distribution in uRPL patients treated with PRS; thus, the treatment re-established the immune system presumed to be beneficial for embryo implantation 21–24. The same effects have been observed in uRPL patients treated with IVIg 22 25–27.…”

Section: Introductionmentioning

confidence: 53%

Intravenous immunoglobulin and prednisolone to women with unexplained recurrent pregnancy loss after assisted reproductive technology treatment: a protocol for a randomised, double-blind, placebo-controlled trial

et al. 2022

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“…It has been demonstrated to be safe and effective in treating pregnancycomplicated immune diseases. 19,20 Regarding nutrient supplements, multivitamin containing folic acid reduces birth defects, especially malformation of the fetal neural tube. 21 Due to the limited efficacy of these single therapies in reducing the risk of spontaneous abortion, combination therapies have been designed and validated to improve live birth rate among women with URSA.…”

Section: Discussionmentioning

confidence: 99%

“…Prednisone is a glucocorticoid with immunosuppressive characteristics that is considered to prevent maternal immune rejection of the zygote during embryo implantation. It has been demonstrated to be safe and effective in treating pregnancy‐complicated immune diseases . Regarding nutrient supplements, multivitamin containing folic acid reduces birth defects, especially malformation of the fetal neural tube …”

Section: Discussionmentioning

confidence: 99%

Efficacy of aspirin, prednisone, and multivitamin triple therapy in treating unexplained recurrent spontaneous abortion: A cohort study

2019

Intl J Gynecology & Obste

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Objective To assess the efficacy of aspirin, prednisone, and multivitamin triple therapy in treating unexplained recurrent spontaneous abortion (URSA). Methods Data were reviewed from women with early RSA attending a hospital in Beijing, China, 2013–2017. Those with no abnormal indices (e.g., endocrine, coagulation, immune, genetic) were diagnosed as having URSA, and received aspirin, prednisone, and multivitamin therapy (triple therapy group, n=106) or folic acid monotherapy (control group, n=65). Treatment efficacy was evaluated as the rate of successful treatment (12‐week pregnancy with obvious embryo and embryonic heart, nuchal translucency thickness <0.25 cm, size consistent with gestational age, no early malformation). Results Overall, 362 women had early RSA and 171 (47.2%) had URSA. The rate of successful pregnancy was similar between the triple therapy (89.6%) and control (92.3%) groups (P=0.343). The rate of successful treatment was higher in the triple therapy (86.3%) than in the control (53.3%) group (P<0.001). In multivariate logistic regression analysis, triple therapy was associated with higher odds of successful treatment, whereas the number of spontaneous pregnancy losses was associated with lower odds of successful treatment. Conclusion The triple therapy of aspirin, prednisone, and multivitamin was found to be a good treatment option for women with URSA.

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“…The corticosteroid prednisone is clinically used in a variety of immune-related diseases and can promote the function and expansion of Tregs (Fu et al 2019). Indeed, in vitro prednisone treatment increased the proportion of Tregs among isolated first trimester decidual lymphocytes and inhibited Th17 cells (Fu et al 2017). Moreover, a clinical trial provided evidence that prednisone increased peripheral Tregs and improved pregnancy success in repeated implantation failure patients (Huang et al 2021).…”

Section: R26mentioning

confidence: 99%

The immunobiology of preterm labor and birth: intra-amniotic inflammation or breakdown of maternal–fetal homeostasis

et al. 2022

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Preterm birth, the leading cause of neonatal morbidity and mortality worldwide, results from preterm labor, a syndrome that includes multiple etiologies. In this review, we have summarized the immune mechanisms implicated in intra-amniotic inflammation, the best-characterized cause of preterm labor and birth. While the intra-amniotic inflammatory responses driven by microbes (infection) or alarmins (sterile) have some overlap in the participating cellular and molecular processes, the distinct natures of these two conditions necessitate the implementation of specific approaches to prevent adverse pregnancy and neonatal outcomes. Intra-amniotic infection can be treated using the correct antibiotics, whereas sterile intra-amniotic inflammation could potentially be treated using a combination of anti-inflammatory drugs (e.g., betamethasone, inflammasome inhibitors, etc.). Recent evidence also supports a role for fetal T-cell activation as a newly described trigger for preterm labor and birth in a subset of cases. Moreover, here we also provide evidence of two potential immune mechanisms responsible for a subset of preterm births formerly considered to be idiopathic. First, the impairment of maternal Tregs can lead to preterm birth, likely due to the loss of immunosuppressive activity resulting in unleashed effector T-cell responses. Second, homeostatic macrophages were shown to be essential for maintaining pregnancy and promoting fetal development, and the adoptive transfer of homeostatic M2-polarized macrophages shows great promise for preventing inflammation-induced preterm birth. Collectively, in this review, we discuss established and novel immune mechanisms responsible for preterm birth and highlight potential targets for novel strategies aimed at preventing the multi-etiological syndrome of preterm labor.

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Prednisone may induce immunologic tolerance by activating the functions of decidual immune cells in early pregnancy

Cited by 9 publications

References 27 publications

Intravenous immunoglobulin and prednisolone to women with unexplained recurrent pregnancy loss after assisted reproductive technology treatment: a protocol for a randomised, double-blind, placebo-controlled trial

Intravenous immunoglobulin and prednisolone to women with unexplained recurrent pregnancy loss after assisted reproductive technology treatment: a protocol for a randomised, double-blind, placebo-controlled trial

Efficacy of aspirin, prednisone, and multivitamin triple therapy in treating unexplained recurrent spontaneous abortion: A cohort study

The immunobiology of preterm labor and birth: intra-amniotic inflammation or breakdown of maternal–fetal homeostasis

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