Exploreing The Effect Of Prednisone On Maternal-fetal Immune Regulation From IL-23/IL-17 Axis

Objective Our previous study found that,Th17 cells and Th17-related cytokines interleukin-17(IL-17)and IL-23 levels in peripheral blood and decidual tissues of patients with unexplained recurrent spontaneous abortion(URSA)were significantly higher than those in normal pregnancy person.As a classic inflammation axis,IL-17/IL-23 plays an important role in the pathological process of infectious diseases,autoimmune diseases and cancer,and become a new target for the treatment of autoimmune diseases,while URSA is thought to be related to maternal fetal immune imbalance.Prednisone was used in the treatment of recurrent embryo transfer failure and URSA,but it was not widely accepted.In this study,we use mouse spleen lymphocytes as the experimental object,through the method of cells culture in vitro,application the cell factor TGF-beta 1,IL-6,IL-23 to stimulate lymphocyte differentiation to Th17 cell to simulation the maternalfetal immune rejection,than to observe the effects prednisone on IL-17 secretion and the regulating effect on IL-17/IL-23 axis,to explore the mechanism of prednisone on the treatment of unexplained recurrentspontaneous abortion and recurrent abortion may,In order to provide basic theory for prednisone on the treatment of failure pregnancy.Method Splenocytes were isolated in vitro and stimulated by anti-CD3 and anti-CD28.Effects of different concentrations of prednisone on proliferation of spleen lymphocytes were tested by MTT test.In the further experiment,group A cells cultured with blank culture medium?group B cultured with prednisone containing culture medium and all cultured for 24 h,then change culture medium containing TGF-?1,IL-6and IL-23 for another 48 h.C,D group lymphocytes were culture in medium containing TGF-?1,IL-6 and IL-23 for 48 h,then C group use medium containing prednisone and group D use blank medium cultured for another 24 h.After 72 h,the secretion of IL-17 a in the supernatant of differernt grops were determined by ELISA.The expression of IL-17 mRNA and IL-23 mRNA in cells were determined by fluorescence-based real time quantitative transcription(RT-PCR).Results MTT outcome showed that the ability of splenocytes proliferation inhibit in a low prednisone concentration compared with the blank group(P < 0.05).The effects of differernt prednisone concentration within the range of 0.001-10 uM on cells have no significant,when the concentration is greater than 100 u M,cells are subjected to significantly inhibited.The secretion of IL-17 a of B group is lower then A group,C group is lower then D group(P<0.01),The expression level of IL-17mRNA have The same trend.While the IL-23 mRNA expression has no significant between B and A,but C group was significantly lower than that of D group(P<0.01).Conclusion Prednisone could inhibit lymphocyte proliferation andinhibit the differentiation of Th17 cells and Th17 related cytokines IL-17,it may exerts anti-inflammatory and immuneregulation effect through inhibiting IL-23/IL-17 aixs.It can be inferred that,prednisone can inhibit the differentiation of Th17 cells,downregulate the expression of Th17-related cytokines IL-17,IL-23,so that inhibit the maternal-fetal immune rejection,induced maternal-fetal immune balance,so as to improve the pregnancy rate.