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目的探讨环磷酰胺(CTX)和环孢素A(CsA)对系统性红斑狼疮(SLE)患者外周血单个核细胞(PBMCs)的干扰素(IFN)-γ、白细胞介素(IL)-10、γ干扰素诱生肽(IP)-10和IL-12分泌水平和T亚群细胞的影响。方法 16例不同SLE疾病活动指数(SLEDAI)的SLE患者和12名正常对照的PBMCs分空白孔、植物血凝素(PHA)刺激孔、PHA+CsA孔、CsA孔、PHA+CTX孔、CTX孔行体外细胞培养,应用酶联免疫吸附法检测血清和PBMCs培养上清IFN-γ、IL-10、IL-12 P40+P70和IP-10分泌水平。同时,对10例重度活动的SLE患者和6名正常对照的PBMCs,采用上述给药方案体外培养后,利用三色流式细胞术检测 CD4+IFN-γ-IL-10+T细胞、CD4+IFN-γ+IL-10-T细胞和CD4+IFN-γ+IL-10+T细胞的百分率。结果与对照组相比,SLE患者血清及PBMCs培养中IFN-γ、IL-10、IL-12和IP-10水平不同程度增高,同时PBMCs中表达CD4+IFN-γ-IL-10+T细胞、CD4+IFN-γ+IL-10-T细胞和CD4+IFN-γ+IL+10+T细胞比例明显增高(P< 0．05),CsA及CTX均能抑制SLE PBMCs培养中IL-10水平,并对PHA刺激下的IFN-γ、IP-10和IL-12 分泌增高有抑制作用,且CsA的抑制作用更为显著;同时CsA还能显著抑制活化状态下PBMCs中表达 CD4+IFN-γ-IL-10+T细胞和CD4+IFN-γ+IL-10+T细胞比例增高(P<0．05)。结论 SLE患者体内存在Th1 和Th2共同参与的复杂的细胞因子网络失衡。CsA与CTX均能干扰SLE细胞因子网络失调的免疫病理过程,且CsA的调节作用更为显著。与CTX相比,应用CsA可以更有效地改善患者的病情。
Objective To investigate the effects of cyclophosphamide (CTX) and cyclosporine A (CsA) on the expression of interferon (IFN) -γ, interleukin (IL) -10 in peripheral blood mononuclear cells (PBMCs) from patients with systemic lupus erythematosus , Interferon-inducible peptide (IP) -10 and IL-12 secretion and T subpopulations. Methods 16 cases of SLE patients with different SLE disease index (SLEDAI) and 12 normal control PBMCs were divided into blank holes, PHA stimulation holes, PHA + CsA holes, CsA holes, PHA + CTX holes and CTX holes In vitro cell culture, the secretion of IFN-γ, IL-10, IL-12 P40 + P70 and IP-10 in serum and PBMC culture supernatants were detected by enzyme-linked immunosorbent assay. At the same time, PBMCs from 10 severe SLE patients and 6 normal controls were cultured in vitro using the above dosing regimen. The levels of CD4 + IFN-γ-IL-10 + T cells and CD4 + IFN-γ + IL-10-T cells and CD4 + IFN-γ + IL-10 + T cells. Results Compared with the control group, the levels of IFN-γ, IL-10, IL-12 and IP-10 in serum and PBMCs of SLE patients increased to different extents, while the expression of CD4 + IFN-γ-IL-10 + T cells in PBMCs , The proportion of CD4 + IFN-γ + IL-10-T cells and CD4 + IFN-γ + IL + 10 + T cells was significantly increased Level, and inhibited the secretion of IFN-γ, IP-10 and IL-12 under the stimulation of PHA, and the inhibitory effect of CsA was more significant. CsA also significantly inhibited the expression of CD4 + IFN- The proportion of γ-IL-10 + T cells and CD4 + IFN-γ + IL-10 + T cells increased (P <0.05). Conclusions Th1 and Th2 are involved in complex cytokine network imbalance in SLE patients. Both CsA and CTX can interfere with the immunopathological process of SLE cytokine network disorders, and the regulation effect of CsA is more significant. Compared with CTX, the application of CsA can be more effective in improving the patient’s condition.