ABSTRACT
Background and Aim: The Th17/Treg balance in peripheral blood and reproductive tissues may have a role in the etiology of unexplained recurrent pregnancy loss (URPL). In this study, we evaluated the major cytokine of Treg cells transforming growth factor-beta (TGF-ß), and their specific transcription factor Forkhead box P3 (FOXP3), as well as the most highlighted cytokine of Th17 cells (interleukin [IL]-17A) in both URPL patients and healthy women. Methods: Samples were extracted from the peripheral blood, endocervix, endometrium, and vagina of 14 patients with URPL and 12 normal non-pregnant women as a control (normal) group. Quantitative reverse transcription polymerase chain reaction was used to determine gene expression. Enzyme-linked immunosorbent assay was used to determine the levels of cytokines in the serum and cervicovaginal fluid. Results: We found that in the URPL group, FOXP3 gene expression was considerably higher in peripheral blood than in the normal group (P=0.043). TGF-ß levels in the cervicovaginal fluid were different in the URPL and normal groups (P=0.015). In comparison to the control group, women with URPL had significantly greater IL-17 gene expression in the peripheral blood (P=0.01). Conclusion: Lower TGF-ß levels in the cervicovaginal fluid of patients compared to controls may be related with increased IL-17 and FOXP3 mRNA levels in patients with URPL. Dysregulation of local immune responses in reproductive tissues may represent dysregulation of systemic regulatory immunological responses in the pathogenesis of URPL. Relevance for Patients: Dysregulation of immune responses may play a role in the pathogenesis of URPL at least in some patients with URPL. We conclude that the breakdown of tolerance in the local immune responses is more critical than the breakdown of tolerance in systemic tolerance in the pathogenesis of URPL. Therefore, modulating immune responses in the endometrium and decidua may be the focus of future therapeutic approaches in URPL. The impact of seminal plasma on the expansion of Tregs may provide a novel therapeutic intervention that has already been used in assisted reproductive technologies. Therefore, we suggest that transvaginal TGF-ß in women with URPL may induce maternal tolerance which leads to the successful pregnancy.
ABSTRACT
Multiple sclerosis (MS) and experimental autoimmune encephalomyelitis (EAE), an animal model of MS, are diseases resulting in neurological disabilities that are regarded as chronic, inflammatory, and autoimmune diseases of central nervous system (CNS). In this respect, the use of anti-inflammatory compounds including flavonoids, polyphenolic compounds abundantly found in vegetables and fruits, has proposed to combat MS to dampen the inflammation and thereby ameliorating the disease severity. The objective of this study was to clarify the probable therapeutic effect of flavonoids for treatment of MS. Therefore, only English published articles that reported the therapeutic effect of flavonoids alone or in combination with other anti-MS therapeutic agents on MS, were selected by searching scientific electronic databases including PubMed, Scopus and Web of Science. Evaluation of the selected researches (686) showed that a total of 13 studies were suitable to be included in this systematic review. Interestingly, all of the studies (11 studies concerning EAE and 2 studies concerning MS) reported positive outcomes for the therapeutic effect of flavonoids on EAE and MS. All flavonoid compounds which are mentioned herein could successfully decrease the maximum clinical score of EAE, which is particularly connected to the anti-inflammatory property of these compounds. The literature review clearly discloses that flavonoids alone or in combination with other anti-MS therapeutic agents can pave the way for improving MS therapeutic strategies.
