Effect Of Bushenyisui Capsules On Clinical Efficacy And Immune Function Of Neuromyelitis Optica Spectrum Disease During Remission

Objective: Neuromyelitis optica spectrum disorders(NMOSD),as a demyelination disease occurring in the central nervous system,has sever clinical nervous function deficiency causing by optica nerve and spinal cord injury.The purpose of this study was to observe clinical efficacy and immune function of Bu Shen Yi Sui(BSYS)capsules on NMOSD during remission.The anti-apoptosis genes Bcl-2 and its promoter signal(nuclear factor kappa-light-chain-enhancer of activated B cells,NF-?B)in CD4+ T cells,epithelial neutrophil-activating peptide(ENA)78,IL-1? and TNF-? in multiple sclerosis(MS)and NMOSD patients were evaluated.Methods: Healthy subjects(HS,n = 25),patients with MS(n = 25)and NMOSD(n = 31)in remission were consecutively enrolled in this prospective study between September,2014 and September,2015.All subjects' information including age,age of first onset,disease duration and relapse times was recorded and analyzed.Expanded disability status scale(EDSS)and Chinese traditional medicine symptom(TCMS)scores were assessed by a cohort researchers.CD4+ T cells were isolated using magnetic beads coated with anti-CD4 monoclonal antibodies,and gene expression of Bcl-2,NF-?B,phosphatidylinositol-4,5-bisphosphate 3-kinase/protein kinase B(PI3K/Akt),and MAP kinase kinase kinase 7(MAP3K7)was measured by real time fluorescent quantitative reverse transcription polymerase chain reaction(Realtime rt PCR).Cytokines of ENA 78,tumor necrosis factor(TNF)-? and interleukin(IL)-1? were detected using human cytokine multiplex assay.Meanwhile,CD4+CD25+ T cells,CD8+ T cells,CD4+PD1+CXCR5+ T cells in peripheral blood of NMOSD patientswere counted by cytometry.Plasma levels of IL-6,IL-17 A,TNF-?,TGF-?1,INF-? and others were detected using human cytokine multiplex assay.The mi RNAs were screened by gene chip technique and the selected genes were verified by Taqman probe method.Results: Plasma levels of ENA 78 were significantly higher in NMOSD patients than in HC(P < 0.001)and MS patients(P < 0.05).The NMOSD patients showed higher plasma levels of IL-1? compared with HC(P < 0.01).Further,increased plasma levels of TNF-? were found in the MS(P < 0.05)and NMOSD patients(P < 0.001).In addition,NMOSD patients had higher EDSS scores compared with MS patients(P < 0.05).EDSS scores were correlated with plasma levels of ENA 78 in NMOSD patients(P < 0.05).There were no significant correlations between EDSS scores and plasma levels of ENA 78 in MS patients(P > 0.05).Bcl-2 and NF-?B gene expressions were elevated in NMOSD patients(1.63 ± 0.25;2.35 ± 0.25)compared with those of HS(0.90 ± 0.11;1.42 ± 0.22)and/or MS patients(1.03 ± 0.18;1.55 ± 0.20)(P < 0.05).MAP3K7,but not Akt,was increased in NMOSD patients(1.23 ± 0.18;1.56 ± 0.22)(P < 0.01)and was a significant factor related to elevated NF-?B gene expressions(P < 0.001).On the other hand,IL-1? and TNF-? were also detected in the study and the results showed that both were elevated in NMOSD patients(23.84 ± 1.81;56.40 ± 2.45)(P < 0.01;P < 0.05,respectively).In NMOSD patients,the portion of CD4+CD25+ T cells in peripheral blood was upregulated by BSYS capsules treatment.The CD4+CXCR5+PD1+ T cells and CD8+ cells were cut down with BSYS treatment.The levels of cytokines as ENA-78,IL-6,IL-17 A,TNF-? and TGF-?1 were down regulated by BSYS capsules and cytokines levels as IL-23,IL-4,IL-17 E,IL-1?,INF-?,IL-2 and IL-33 did not change with 3 months BSYS capsules treatment.Conclusion: The overproduction of pro-inflammatory cytokines such as IL-1? and TNF-? during the remission of NMOSD activates ENA 78,which in turn leads toneutrophil infiltration in lesions.ENA 78 plasma levels were correlated with EDSS scores in NMOSD patients.Elevated secretion of ENA 78 may be a critical step in neutrophil recruitment during the remission of NMOSD.We propose that MAP3K7 induced by IL-1? and TNF-? but not Akt promotes NF-?B expression and,in turn,prolongs Bcl-2–mediated survival of CD4+ T cells in NMOSD patients.BSYS capsules have the ability of alleviating the immune pathogenesis by regulating cytokines levels in peripheral blood to reduce neurological defects with NMOSD patients.