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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.
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).
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.
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.El texto completo de este artículo está disponible en PDF.
Keywords : Hydroxychloroquine, IL-10, Repeated implantation failure, TNF-α, IL-4, IFN-γ