Immunomodulatory effects of hydroxychloroquine on Th1/Th2 balance in women with repeated implantation failure

• Published in: Biomedicine & pharmacotherapy 2018-11, Vol.107, p.1277-1285
• Main Authors: Ghasemnejad-berenji, H., Ghaffari Novin, M., Hajshafiha, M., Nazarian, H., Hashemi, S.M., Ilkhanizadeh, B., Ghasemnejad, T., Sadeghpour, S., Ghasemnejad-berenji, M.
• Format: Article
• Language: English
• Subjects: Adult; Embryo Implantation - drug effects; Embryo Implantation - immunology; Female; Fertilization in Vitro - methods; Humans; Hydroxychloroquine; Hydroxychloroquine - pharmacology; IFN-γ; IL-10; IL-4; Immunomodulation - drug effects; Interleukin-10 - blood; Pregnancy; Recurrence; Repeated implantation failure; Th1 Cells - drug effects; Th1 Cells - immunology; Th2 Cells - drug effects; Th2 Cells - immunology; TNF-α; Treatment Failure; Tumor Necrosis Factor-alpha - blood
• ISSN: 0753-3322; 1950-6007
• DOI: 10.1016/j.biopha.2018.08.027

[Display omitted] •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. 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. 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). Hydroxychloroquine treatment significantly decreased (p