Abstract

BIOPHARMACEUTICAL IMPACT OF VAGINAL SILDENAFIL CITRATE THERAPY ON SOME INFLAMMATORY CYTOKINES AND T/NK CELLS SUBSETS IN UNEXPLAINED RECURRENT SPONTANEOUS MISCARRIAGE: FIRST LONGITUDINAL CLINICAL STUDY OF 50 CASES FROM EGYPT

Mohamed El-Far *, Abd El- awad El-Motwally , Ikbal Abou Hashem, Dalia Salem,Nadia Bakry

ABSTRACT

Various immunological abnormalities have been reported in women with unexplained recurrent spontaneous miscarriage (URSM). The definition of pregnancy as a "TH2" or anti-inflammatory state was proved by numerous studies and a shift in TH2 cytokines (e.g. IL-4, IL- 6, IL-10) towards TH1 cytokines (TNF-α, IFN-γ) may be a potential relevant factor in RSM. In a previous study, we were the first to show the novel biopharmaceutical use of vaginal sildenafil citrate (SC) in treatment of URSM. The aim of this study is to evaluate the effect of vaginal SC tablet administration at different doses on the NK and Tcell subsets (as evaluated by CD3, CD4, CD8, CD16, and CD56 expression) and on some pro- and anti-inflammatory cytokines (TNF-α, IL-6 and IL-10) in patients with first trimester URSM in a longitudinal clinical study and to correlate this with successful pregnancy outcome. We investigated the effects of vaginal SC on some immunological abnormalities found in F-URSM, the study was conducted on two groups of patients in addition to a control group a control group. The first patient group (F-URSM1) received SC at a dose of 25 mg intravaginally, 4 times/day for 24 days ( n= 20), while thesecond patient group (F-URSM2) received SC at a dose of 25 mg intravaginally, 3 times/day for 13 days, (n= 20). The control group comprised of 10 matched first trimester normal pregnant (FTP). Patients also received their usual treatment used in their previous pregnancies ended with miscarriages. ). The percentage of T-cells subsets, CD16+/CD56+ NK cells, TNF-α producing cells, as well as serum IL-6 and IL-10 levels were determined in patient and control groups. Intravaginal SC treatment increased the pregnancy success rate that was more observed in F-URSM1 (65%) than in the F-URSM2 (55%) patients groups. Moreover, different doses significantly increased IL-10 level in the patients under investigation, while the percentage of TNF- α producing cells and CD56+/CD16+ NK cells in peripheral blood were significantly decreased after SC treatment. In conclusion, the use of intra-vaginal SC as anti-abortive agent in URSM patients is partly due to its ability to correct the percentage of TNF-α producing cells, NK cells), and IL-10. Accordingly, SC may offer a potential pharmaceutical therapeutic strategy through ameliorating various immunological abnormalities that might contribute to URSM. Key words: Sildenafil citrate; TNF-α; Cluster of differentiation (CD); Interleukins; NK-cells; Unexplained recurrent spontaneous abortion.

Keywords: Sildenafil citrate; TNF-?; Cluster of differentiation (CD); Interleukins; NK-cells; Unexplained recurrent spontaneous abortion.