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Immunomodulatory effects of hydroxychloroquine on Th1/Th2 balance in women with repeated implantation failure - 20/09/18

Doi : 10.1016/j.biopha.2018.08.027 
H. Ghasemnejad-berenji a, M. Ghaffari Novin a, b, , M. Hajshafiha c, H. Nazarian a, d, S.M. Hashemi e, B. Ilkhanizadeh f, T. Ghasemnejad g, S. Sadeghpour c, M. Ghasemnejad-berenji h
a Department of Biology and Anatomical Sciences, School of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran 
b Infertility and Reproductive Health Research Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran 
c Department of Obstetrics & Gynecology, School of Medicine, Urmia University of Medical Sciences, Urmia, Iran 
d IVF Center, Taleghani Educational Hospital, Shahid Beheshti University of Medical Sciences, Tehran, Iran 
e Department of Immunology, School of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran 
f Department of Pathology, Faculty of Medicine, Urmia University of Medical Sciences, Urmia, Iran 
g Department of Medical Genetics, Faculty of Medicine, Tabriz University of Medical Sciences, Tabriz, Iran 
h Department of Pharmacology and toxicology, Faculty of Pharmacy, Urmia University of Medical Sciences, Urmia, Iran 

Corresponding author at: Department of Biology and Anatomical Sciences, School of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran.Department of Biology and Anatomical SciencesSchool of MedicineShahid Beheshti University of Medical SciencesTehranIran

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Graphical abstract




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Highlights

Elevated Th1/Th2 ratio increases cytotoxicity against embryo and leads to implantation failure.
Hydroxychloroquine significantly reduces TNF-α/IL-10 ratio.
Th1/Th2 balance is affected by hydroxychloroquine in elevated Th1/Th2 ratio.
Hydroxychloroquine shifts the responses toward Th2 and decreases the Th1/Th2 ratio.
Hydroxychloroquine can be an effective treatment for repeated implantation failure in women with immune cell abnormalities.

Le texte complet de cet article est disponible en PDF.

Abstract

Background

Cellular immune abnormalities such as the imbalance between T-helper (Th) 1 and Th2 cytokines have been implicated as potentially modifiable causes of idiopathic repeated implantation failures (RIF). The purpose of this study was to investigate the effects of hydroxychloroquine on IL-10 and TNF-α secretion, expression of T-bet and GATA-3 transcription factors and cellular localization of TNF-α, IFN-γ, IL-10 and IL-4 in endometrial cells in women with RIF.

Materials and methods

A total of 17 women with a history of RIF and elevated TNFα/IL-10 ratio (TNFα/IL-10> = 30.6) were included in the study. The serum levels of TNFα and IL-10, the expression of transcription factors related to Th1 and Th2 cells and the immune-reactivity of TNFα, IFN-γ as Th1 related cytokines and IL-10, IL-4 as Th2 related cytokines in endometrial tissues were evaluated by ELISA, real-time PCR, and fluorescent immunohistochemistry respectively. All, evaluations were done both before and after treatment with hydroxychloroquine (400 mg/orally per day).

Results

Hydroxychloroquine treatment significantly decreased (p < 0.0001) serum level of TNF-α and significantly increased serum level of IL-10 (p < 0.0001). T-bet, the Th1 transcription factor, expression was down-regulated and GATA-3, the Th2 transcription factor, expression was up-regulated. IL-10 and IL-4 fluorescent immunoreactivities significantly increased (p < 0.05 and p < 0.001 respectively) and TNFα and IFN-γ fluorescent immunoreactivities significantly decreased (p < 0.05) in endometrial tissue in women with RIF after treatment in comparison with before treatment.

Conclusion

Hydroxychloroquine administration in women with RIF With a high TNF-α/IL-10 ratio during the implantation window can decrease this ratio and seems to be an effective therapeutic strategy in RIF caused by cellular immune abnormalities through a shift in Th2 responses.

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Keywords : Hydroxychloroquine, IL-10, Repeated implantation failure, TNF-α, IL-4, IFN-γ


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Vol 107

P. 1277-1285 - novembre 2018 Retour au numéro
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