| BackgroundSystemic lupus erythematosus（SLE）is a kind of multiple organ damage autoimmune diseases,which is the result of the interaction between a series of immune system disorders.The etiology and pathogenesis of SLE is still unknown,it may be associated with genetic,infectious,environmental,sex hormones,drugs and other factors,the pathogenesis involving T lymphocytes,B lymphocytes,monocytes,and complement system abnormalities of the immune components.It is currently considered that lymphocyte abnormal activation of the immune system is the key of the pathogenesis,disease progression and prognosis of SLE.Studies have shown that cytokines which T help cells（Th）produce play an important role in the pathogenesis of SLE and other autoimmune diseases.Activation of autoreactive Th cells promote B cells differentiation to produce autoantibodies[5],in addition,immune complexes containing autoantibodies and inflammatory Th cells cause tissue and organ damage.As early as 1986,Momann and Coffman[6]proposed Th1/Th2 cell subsets hypothesis,that Thl and Th2 cells is divided into two subsets depending on the cell differentiation,functional characteristics and cytokine secretion,the specificity of CD4+ Th cells,that generate the theoretical framework of understanding the biology of CD4+T cell immunity,innate and adaptive immune regulation.Th1 cells mainly secrete interleukin（IL）-2、interferon-gamma（IFN-γ）,that IL-12 induced to differentiate of,the function is to enhance the cellular immune effects.Th2 cell differentiation depends on IL-4,mainly secreting IL-4、IL-5、IL-9 and IL-13,which play an important role in the humoral immune response.Thl-type immune response disorders can lead to tissue damage and chronic inflammation,while Th2-type immune response disorders may cause asthma and allergy[7,8].For a long time,most scholars believe that the imbalance between Th1/Th2 lead to the occurrence of autoimmune diseases[9].Early studies suggest that SLE is a disease of one kind of Th2 cell polarization,specifically to produce autoantibodies against autoantigens[10].By some studys,Th1 cell responses of SLE patients is enhanced,including IL-2,IFN-γ increased[11].In the past,people generally believe in the process of T cells mediated immune response,mainly caused by Th1 cells or Th2 cells[13].In recent years,with the discovery of a new T cell subset-Th17 cells,the Th1/Th2 theory is undergoing major changes.Tn17 cells are a new group of CD4+ T cells,that humans found in the study of animal models of autoimmune diseases such as experimental autoimmune encephalomyelitis[14]（EAE）and collagen-induced arthritis[15]（CIA）.Now believed that Th17 cells are secreted by an independent of CD4+ T cell subsets,these cells represent a pro-inflammatory Th cell lineage,different from the traditional Th1 cells or Th2 cells.They are not expression of IFN-y or IL-4,but high expression of IL-17,so was named Th17 cells[16].Th17 cells play an important role in the defensive cells of pathogenic microorganisms infections、chronic inflammation and autoimmune diseases,which is currently one of the focus.It is Currently considered IL-23--Th17 axis that is the core factor for autoimmune diseases plays a key role in the development and the occurrence of autoimmune diseases.The role of Th17 cells in the pathogenesis of SLE has become one of the hotspots at home and abroad.Many studies have shown that Th17 cells may be the key effector cells of SLE,IL-17 and other cytokines also has an important influence in the occurrence and development of SLE[29].Most of the time,long-term use hormones、immunosuppressants and other antirheumatic drugs in order to control SLE for patients,but many of its toxic side effects limit its clinical application.Because of its good efficacy and no significant adverse reactions,total glucosides of paeony（TGP）has been used in SLE treatment.SLE is a common autoimmune disease,but currently studies of Th17 cells and their cytokines in SLE patients is few,people’s ideas are also inconsistent.Such studies about the influence of TGP on Th17 cells and their cytokines of patients with SLE is not reported.Whether TGP play anti-inflammatory and immunomodulatory effects through Th17 cells regulation and whether Th17 cells is target cells for TGP treatment,is a problem worthy of study.Therefore,this study observe the expression levels change of peripheral blood Th17 cells of patients with SLE before and after utilizing TGP as well as its relevance and significance of the SLE clinical treatment;We also observed the comparison of expression levels of Th17 cells related cytokines IL-17、IL-23 in SLE patients before and after TGP treatment,to research the regulation of Th17 cells and to investigate the immunological mechanisms when treat patients with SLE using TGP.Objective（1）To observe the expression levels influence of peripheral blood Th17 cells of patients with SLE before and after utilizing TGP;To explore the role of Th17 cells in the pathogenesis of SLE and its clinical relevance.（2）To observe the effects of Th17 cell-associated cytokines IL-17、IL-23 levels of patients with SLE before and after utilizing TGP in order to further explore the role of the Th17 cells and their cytokines（IL-17,IL-23）in the pathogenesis of SLE as well as the mechanism of action when treat patients with SLE.MethodsSelect 60 cases of SLE patients in our hospital from March 2010 to September 2011,patients are randomly divided into TGP group and control group.All patients are up to the 1982 revised American College of Rheumatology（ACR）criteria for the classification of SLE,according to the SLE disease activity index（SLEDAI）standard,calculating the SLEDAI score.Someone who has one of following cases is not included in the scopy of sudy:serious heart、lung、liver、kidney and other organs and blood、endocrine system diseases,and except for pregnancy and lactating women、a history of chronic infection,、recent infection、drug allergy、allergies、patients of one month before utilizing TGP cytotoxic immunosuppressive agents,or with other rheumatic diseases（rheumatoid arthritis,Sjogren’s syndrome,mixed connective tissue disease,etc）.The general condition of patients as follows:TGP group of 30 cases,all are female,age is18 to 45 years old,average age is（26.87 ±7.10）years;control group of 30 cases,all are female,age is 18 to 45 years old,average age is（26.87±7.12）years.TGP group:30 patients adopt the clinical routine treatment plus TGP therapy,TGP dose of 0.6g,2/day,the course of 60 days.Control group:30 patients adopt the clinical routine treatment.Collect peripheral venous blood in the fasting,respectively at 0 days and 60 days early morning.（1）Detecting expression levels of Th17 cells in patients with SLE:adopting flow cytometry to detect the expression levels of peripheral blood mononuclear cells（PBMC）Th 17 cells respectively in the two groups before and after TGP treatment,and analyze the differences.（2）Detecting Th17 cell-associated cytokines（IL-17,IL-23）in patients with SLE:adopting enzyme linked immunosorbent assay（ELISA）to detect the levels of IL-17、IL-23 plasma respectively in the two groups before and after TGP treatment,and analyze the differences.Make use of SPSS 13.0 statistical software for statistical analysis,test data with mean±standard deviation（x±s）represents to indicate,adopt independent samples t test and paired sample test and bivariate correlation analysis,the difference was statistically significant when P<0.05.Results（1）Changes of the expression level of Th17 cells,SLEDAI scores,the levels of plasma IL-17,the levels of plasma IL-23 in the two groups.The expression rate of PBMC Th17 cells,SLEDAI scores,the level of plasma IL-17,the level of plasma IL-23 in control group have a significant difference before and after treatment（t values respectively are 4.560,4.871,11.826,8.706;p value all are less than 0.001）,the expression rate of PBMC Th17 cells,SLEDAI scores,the levels of plasma IL-17,the levels of plasma IL-23 after treatment are significantly lower than before treatment.The expression rate of PBMC Th17 cells,SLEDAI scores,the level of plasma IL-17,the level of plasma IL-23 in TGP group have a significant difference before and after treatment（t values respectively are 4.560,4.871,11.826,8.706;p value all are less than 0.001）,the expression rate of PBMC Th17 cells,SLEDAI scores,the levels of plasma IL-17,the levels of plasma IL-23 after treatment are significantly lower than before treatment.（2）Comparison of changes of the expression level of Th17 cells,SLEDAI scores,the levels of plasma IL-17,the levels of plasma IL-23 in the two groups.Decline of the expression rate of PBMC Th17 cells,SLEDAI scores,the levels of plasma IL-17,the levels of plasma IL-23 in control group and TGP group have a significant difference after treatment（t values respectively are 2.112,2.210,2.450,2.130;p value respectively are 0.039,0.031,0.017,0.037）,the expression rate of PBMC Th17 cells,SLEDAI scores,the levels of plasma IL-17,the levels of plasma IL-23 in TGP group are significantly higher than control group after treatment.（3）The correlation analysis of expression level of Th17 cells,the level of plasma IL-17,the level of plasma IL-23 and SLEDAI scores before treatment in the two groups.The expression rate of PBMC Th17 cells,the level of plasma IL-17,the level of plasma IL-23 and SLEDAI scores are not significant correlation before treatment in control group（r value respectively are-0.073,0.123,0.103;p value respectively are 0.703,0.519,0.588）.The expression rate of PBMC Th17 cells,the level of plasma IL-17,the level of plasma IL-23 and SLEDAI scores are not significant correlation before treatment in TGP group（r value respectively are-0.005,0.052,0.042;p value respectively are 0.980,0.783,0.826）.（4）The correlation analysis of expression level of Th17 cells,the level of plasma IL-17,the level of plasma IL-23 and SLEDAI scores after treatment in the two groups.The expression rate of PBMC Th17 cells and SLEDAI scores are not significant correlation after treatment in control group（r value is 0.353;p value is 0.055）.The level of plasma IL-17,the level of plasma IL-23 and SLEDAI scores show a positive linear correlation after treatment in control group（r value respectively are 0.711,0.712;p value all are less than 0.001）.The expression rate of PBMC Th17 cells,the level of plasma IL-17,the level of plasma IL-23 and SLEDAI scores all show a positive linear correlation after treatment in TGP group（r value respectively are 0.449,0.772,0.808;p value respectively are 0.013,<0.001,<0.001）.（5）The correlation analysis of the level of plasma IL-17 and the level of plasma IL-23 before and after treatment in the two groups.The level of plasma IL-17 and the level of plasma IL-23 are not significant correlation before treatment in control group（r value is-0.196;p value is 0.299）.The level of plasma IL-17 and the level of plasma IL-23 show a positive linear correlation after treatment in control group（r value is 0.743;p value is<0.001）.The level of plasma IL-17 and the level of plasma IL-23 are not significant correlation before treatment in TGP group（r value is-0.314;p value is 0.091）.The level of plasma IL-17 and the level of plasma IL-23 show a positive linear correlation after treatment in TGP group（r value is 0.799;p value is<0.001）.ConclusionsExpression rate of Th 17 cells、the SLEDAI scores、the levels of plasma IL-17 and IL-23 are significantly lower when treat patients with SLE after utilizing TGP.The results suggest that:①The Th17 cells in the pathogenesis of SLE may play an important role,Th17 cells and related cytokines may be involved in the pathophysiological process of SLE development,tiological targeted therapy for Th17 cells may be a new effective method for the treatment of SLE;② TGP can regulate the immune function of patients with SLE and achieve the purpose through IL-23/Th17 axis in treating SLE. |
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