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

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-alpha secretion, expression of T-bet and GATA-3 transcription factors and cellular localization of TNF-alpha, IFN-gamma, 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 TNF alpha/IL-10 ratio (TNF alpha/IL-10> = 30.6) were included in the study. The serum levels of TNF alpha and IL-10, the expression of transcription factors related to Th1 and Th2 cells and the immune-reactivity of TNF alpha, IFN-gamma as Th1 related cytokines and IL10, 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-alpha 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 TNF alpha and IFN-gamma 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-alpha/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.