重症肌无力患者血清可溶性白细胞介素—2受体的研究

应用酶联免疫吸附法 ( ELISA)测定 4 7例重症肌无力 ( MG)患者和 2 2例健康对照者血清中可溶性白细胞介素 - 2受体 ( s IL- 2 R)水平 ,结果发现 MG患者血清 s IL- 2 R水平明显高于健康对照组 ( P<0 .0 0 5,P<0 .0 0 1) ,且各型之间亦具有显著性差异 ( P<0 .0 0 1)。病情越重 ,临床记分越高 ,s IL - 2 R水平越高 ;免疫抑制剂治疗后较治疗前明显下降 ,临床记分与 s IL - 2 R滴度呈正相关。认为对 MG患者血清 s IL -2 R的测定 ,有助于对该病进行动态观察 ,可作为判断病情的客观指标     

急性Guillain—Barre综合征患者血清sIL—2R和sIL—6R水平 …

目的　探讨可溶性白细胞介素 2受体 (s IL- 2 R)和可溶性白细胞介素 6受体 (s IL- 6 R)在急性Guillain- Barre综合征 (GBS)发病中的作用。方法　采用 EL ISA方法测定 32例 GBS患者和 30名正常对照者血清 s IL- 2 R及 s IL- 6 R水平。结果　 GBS患者血清 s IL- 2 R和 s IL- 6 R水平明显高于正常对照组 (P<0 .0 1,P<0 .0 5 ) ,重型和极重型患者明显高于轻型及中型患者 (P<0 .0 1,P<0 .0 5 ) ,且随着病情的好转 ,两种受体水平也逐渐下降 ,与治疗前比明显下降 (均 P<0 .0 5 )。结论　 s IL- 2 R和 s IL- 6 R水平的高低可作为判断 GBS病情变化的指标之一。     

重症肌无力胸腺单个核细胞白细胞介素-2、白细胞介素-10及其mRNA水平的变化

目的　研究重症肌无力 ( myasthenia gravis,MG)患者胸腺是否存在辅助性 T细胞 ( Th)亚群的免疫活性紊乱。方法　利用亲和层析法自人腓肠肌纯化获得乙酰胆碱受体 ( ACh R)并进行了鉴定 ,然后用其作为特异性抗原 ,经体外培养刺激 5例 MG患者胸腺和外周血单个核细胞 ,酶联免疫吸附分析 ( ELISA)法检测上清液中白细胞介素 -2 ( IL-2 )、白细胞介素 -1 0 ( IL-1 0 )水平 ,狭缝印迹杂交法检测 MG胸腺及外周血 IL-1 0 m RNA的表达。结果　MG胸腺和外周血经 ACh R刺激后 ,其上清液 IL-2水平略高于对照组 ( P>0 .0 5 ) ,经 ELISA法和狭缝印迹杂交法发现 MG外周血 IL-1 0及其 m RNA表达水平均略高于对照组 ( P>0 .0 5 ) ,胸腺则明显高于对照组( P<0 .0 5 )。结论　 MG发病过程中 IL-1 0的异常增高可能发生于转录或转录以上水平 ,其异常表达的机制有待于进一步研究。     

重症肌无力患者免疫治疗过程中sIL-6R的动态演变

目的:探讨可溶性白细胞介素-6受体（sIL-6R）与重症肌无力(MG)的关系。方法:应用酶联免疫吸附试验(ELISA)动态检测76例不同临床类型的MG患者（MG组）在免疫治疗过程中和48名健康对照者(NC组)血清sIL-6R水平,同时检测MG患者血清乙酰胆碱受体抗体(AChRab)水平,并对MG患者病情按许氏评分法进行量化。结果:(1)MG患者血清IL-6R水平明显高于NC组(P＜0.01);其中病程＞1年组患者sIL-6R水平明显高于病程＜6个月组(P＜0.05),后者血清sIL-6R水平在免疫抑制治疗后明显低于治疗前(P＜0.05)。(2)绝对评分≥31分者sIL-6R水平明显高于评分≤15分患者（P＜0.01,及P＜0.05）;绝对评分≤30分者经免疫治疗后,评分较免疫治疗前明显降低(P＜0.05),并且血清sIL-6R水平明显下降(P＜0.05);单用皮质类固醇组在免疫治疗后,绝对评分和血清sIL-6R水平明显下降(P＜0.05)。(3)血清sIL-6R水平与MG患者病情明显相关(R2=0.528)。结论:sIL-6R参与了MG的免疫发病过程,MG患者存在体液免疫功能紊乱;血清sIL-6R可反映MG免疫治疗的效应,血清sIL-6R可作为观察MG病情变化的指标。     

重症肌无力患者血清sIL—2R水平检测

对100例临床确诊为重症肌无力（MG）、血清乙酰胆碱受体抗体阳性的患者进行血清可溶性白细胞介素-2受体（sIL－2R）检测。结果表明：（1）MG患者治疗前血清中sIL-2R水平与正常对照组无显著性差异。其中全身型MG组较正常对照组sIL－2R水平明显增高，但眼肌型MG组与正常对照组间无显著差异；（2）全身型MG组经强的松治疗4周后sIL－2R水平明显下降；（3）胸腺瘤切除术后1年后sIL－2R水平较术前显著降低。上述结果提示sIL－2R水平可能与MG疾病状态有密切关系。     

白细胞介素2及其受体在神经科学中的应用

本文对白细胞介素2(IL-2)在一些神经系统疾病中的应用研究进行了综述。IL-2及其受体的生化及生物学特征已阐明,在脑肿瘤方面,利用IL-2具促T 细胞增殖作用而获得大量肿瘤杀伤细胞而达到治疗目的,在多发性硬化(MS)病灶中发现IL-2分泌细胞及IL-2受体阳性细胞,急性脑炎病灶中发现IL-2受体阳性细胞,CSF 有游离IL-2受体,MS 及肌炎周围血IL-2/IFN-γ/NK 细胞调节环存在缺陷,重症肌无力周围血IL-2分泌功能缺陷,IL-2与上述疾病内在关系在研究为某些疾病的发病机理探讨及寻找新的治疗手段开辟新领域。     

重症肌无力患者外周血T、B淋巴细胞Bcl-2的表达

目的　探讨重症肌无力 (MG)患者外周血单个核细胞Bcl 2蛋白表达及其临床意义。方法　以流式细胞仪双标记免疫荧光方法测定 4 7例临床确诊的MG患者外周血T、B淋巴细胞Bcl 2蛋白表达和CD3 T细胞Bcl 2蛋白表达的平均荧光强度 (MFI)。结果　 ( 1)MG组外周血CD3 、CD4 、CD8 T淋巴细胞和CD19 细胞Bcl 2蛋白表达明显高于对照组 (P <0 .0 1) ,CD3 T细胞蛋白表达Bcl 2的MFI( 0 .572± 0 .177)亦明显高于对照组 ( 0 .170± 0 .147) (P <0 .0 1)。 ( 2 )MG组外周血CD3 、CD4 、CD8 T淋巴细胞及CD19 细胞的Bcl 2蛋白表达与年龄无明显相关 ,而与临床严重程度绝对评分密切相关 (r=0 .63、0 .65、0 .61、0 .78,P <0 .0 5)。CD3 T细胞蛋白表达的MFI与MG患者病程相关密切 (r=0 .62 ,P <0 .0 1)。 ( 3)免疫抑制治疗后MG组临床严重程度绝对评分与淋巴细胞亚群Bcl 2蛋白表达、CD3 T细胞蛋白表达的MFI同步地较治疗前有明显下降 (P <0 .0 1)。结论　外周血淋巴细胞Bcl 2蛋白异常表达对MG发病及临床症状有重要作用。     

NK细胞参与多发性硬化免疫致病的机制

目的　研究多发性硬化 ( MS)患者外周血 ( PB)中自然杀伤 ( NK)细胞的表达。方法　采用流式细胞仪技术 ,检测 1 5例 MS患者以白细胞介素 -1 2 ( IL-1 2 )刺激 NK细胞增殖前后 PB NK细胞的百分率。结果　MS患者PB中 NK细胞百分率明显低于对照组 ( P <0 .0 5 ) ;以不同浓度的 IL-1 2刺激 NK细胞增殖后 NK细胞百分率呈剂量依赖性增加 ,于 5 d时达到峰值 ,但较刺激前明显减少 ( P <0 .0 5 )。结论　 MS患者 PB中 NK细胞的表达明显减少 ,以 CD1 6+ 和 CD5 6+ 细胞减少为主 ;IL-1 2在 1 0 2 U/m L数量级时可对 NK细胞增殖活性产生最佳激活作用。     

脑胶质细胞瘤病人IL-2和sIL-2R表达及细胞免疫功能变化的意义

目的 研究脑胶质细胞瘤病人外周血中自细胞介素2（IL-2）、可溶性白细胞介素2受体（sIL-2R）的表达以及红细胞免疫和T淋巴细胞亚群的变化规律．探讨它们之间的相互关系。方法 对55例脑胶质瘤病人及55例健康献血员．采用酶联免疫吸附（ELISA）法测定血清IL-2、sIL-2R含量，免疫黏附法测定红细胞免疫活性及其调节功能，链亲和素一过氧化物酶（SP）一步法测定CD3、CD4、CD8细胞数。结果 脑胶质细胞瘤组IL-2含量较对照组显著性降低（P〈0.01），sIL-2R则显著性升高（P〈0．01）；红细胞C3b受体（RBC-C3bR）、红细胞免疫调节促进因子（RFER）亦显著性降低（P〈0．01），而红细胞免疫复合物（RBC-ICR）、红细胞免疫调节抑制因子（RFm）则显著性升高（P〈0．01）；CD3、CD4细胞数显著性降低（P〈0．001），而CD8无显著性差异（P〉0．05）。结论 脑胶质细胞瘤病人存在免疫功能低下；检测血清IL-2和sIL-2R含量、红细胞免疫功能及T细胞亚群活性，对脑胶质细胞瘤病人的免疫机制研究具有重要意义。     

髓源树突细胞源性外泌体对实验性自身免疫性重症肌无力大鼠NK及NK T细胞的影响

目的探讨他汀类药物诱导髓源树突细胞(BMDCs)源性外泌体(exosomes)对实验性自身免疫性重症肌无力(EAMG)大鼠自然杀伤细胞(NK)及NK T细胞的影响。方法阿托伐他汀和DMSO分别与BMDCs共培养,采用流式细胞术分析其表型。应用梯度离心法提取不同组BMDCs分泌的外泌体(分别记为他汀Dex和对照Dex),将不同组外泌体注射于EAMG大鼠体内,采用双盲法观察EAMG临床症状;通过流式细胞术检测各组大鼠淋巴结NK、NK T和干扰素γ(IFN-γ)阳性细胞、白细胞介素-10(IL-10)阳性细胞的表达水平;采用ELISA方法检测各组血清抗R97-116IgG抗体及其亚型水平。结果他汀类药物能够明显抑制BMDCs表面CD80和CD86的表达水平(CD80:1.10%比22.80%,P0.01;CD86:30.78%比43.93%,P0.01),这些BMDCs可进一步分泌他汀Dex。与对照Dex治疗组比较,他汀Dex治疗组EAMG大鼠淋巴结NK细胞比例增加(2.30%比1.63%,P0.05),淋巴结单个核细胞(MNC)中IFN-γ+细胞比例(1.05%比2.24%,P0.05)、血清抗R97-116IgG抗体及其亚型IgG2a和IgG2b水平均明显降低(IgG:0.44比0.64,IgG2a:0.26比0.35,IgG2b:1.47比1.94;均P0.05)。结论他汀Dex可缓解EAMG大鼠的临床症状,这种作用与上调淋巴结MNC中的NK细胞有关。     

In-vitro Immunomodulatory Effects of Haloperidol and Perazine in Schizophrenia

Summary: There are some reports describing concurrent changes in lymphocytic and monocytic activities in schizophrenia. In this study we investigated T cell activity in schizophrenic patients by measuring the release of interleukin-2 (IL-2) and soluble interleukin-2 receptor (sIL-2R) by T cells and the percentages of CD4+ and CD8+ cells in blood. The release of IL-2 and sIL-2R by T cells was evaluated in dilute whole blood after in-vitro stimulation with phytohemagglutinin. IL-2 levels and the percentage of CD4-cells tended to decrease and sIL-2R levels decreased significantly in schizophrenic patients. Haloperidol and perazine significantly decreased IL-2 levels and increased sIL-2R levels and the percentage CD4-cells. IL-2 and sIL-2R levels were lower in patients with a predominance of positive symptoms. The neuroleptic-induced increase in sIL-2R levels was higher in patients with a predominance of positive symptoms compared with those in whom both positive and negative symptoms were severe. The study has shown that T-cell activity is reduced in schizophrenia and that neuroleptics may have immunomodulatory properties.     

脑出血患者周围血T淋巴细胞亚群及sIL—2R水平的研究

目的：探讨脑出血患者的细胞免疫功能及其临床意义。方法：对４６例脑出血患者及４２例正常对照组外周血Ｔ淋巴细胞亚群及血清可溶性白细胞介素－２受体（ｓＩＬ－２Ｒ）水平进行检测,并对其中２１例脑出血患者恢复期外周血Ｔ淋巴细胞亚群及血清ｓＩＬ－２Ｒ水平进行了复查。结果：脑出血急性期外周血ＣＤ３数量明显低于对照组,ＣＤ４与对照组比较无显著性差异,ＣＤ８明显高于对照组,ＣＤ４／ＣＤ８比值则显著低于对照组,血清ｓＩＬ－２Ｒ水平显著高于对照组;病情重者、预后差者周围血ＣＤ３数量明显少于病情轻者、预后好者,ＣＤ８数量明显多于病情轻者、预后好者,ＣＤ４／ＣＤ８比值显著低于病情轻重、预后好者,血清ｓＩＬ－２Ｒ水平显著高于病情轻重、预后好者;脑出血组恢复期与急性期比较,周围血ＣＤ３数量明显增多,ＣＤ８明显减少,ＣＤ４／ＣＤ８比值明显升高     

High numbers of circulating activated T cells and raised levels of serum IL-2 receptor in bipolar disorder.

BACKGROUND: Previously, we found an increased prevalence of thyroid autoantibodies in patients with bipolar disorder. In the present study, we investigated other signs of immune activation in bipolar patients, in particular an activation of the T cell system. METHODS: Fluorescence activated cell scanning (FACS) analysis was performed on lymphocytes of 64 outpatients with DSM-IV bipolar disorder using the T cell marker CD3 in combination with the activation markers MHC-class II, CD25, CD69 or CD71. In 34 patients, these assays were repeated after an interval of 2 years. In addition, T cell activation was determined by measuring serum soluble IL-2 receptor (sIL-2R) in 172 bipolar outpatients. Outcomes were compared with a healthy control group. RESULTS: Significantly higher numbers of circulating activated T cells and raised sIL-2R levels were found in euthymic, manic, and depressed bipolar patients when compared with healthy controls. In general, these abnormalities were stable over time. Manic patients showed significantly higher levels of sIL-2R in comparison with depressed patients. CONCLUSION: The T cell system was found to be activated in both symptomatic and euthymic patients with bipolar disorder. The pathophysiological significance of these findings remains to be explored.     

糖皮质激素对重症肌无力患者周围血IL－2活性及sIL－2R水平的影响

检测了４２例重症肌无力（ＭＧ）患者周围血单个核细胞（ＰＢＭＣ）白细胞介素－２（ＩＬ－２）活性及血清可溶性白细胞介素－２受体（ｓＩＬ－２Ｒ）水平，重点观察了１４例ＭＧ患者在糖皮质激素（ＧＣ）治疗后ＩＬ－２活性及ｓＩＬ－２Ｒ水平变化。结果显示，ＭＧ患者ＰＢＭＣＩＬ－２活性显著低于正常对照组，而血清ｓＩＬ－２Ｒ水平显著高于正常对照组，且ＭＧ患者ＩＬ－２活性与ｓＩＬ－２Ｒ水平之间呈显著负相关；应用ＧＣ治疗后，ＩＬ－２活性显著升高，ｓＩＬ－２Ｒ水平显著下降。提示ＭＧ患者ＩＬ－２活性变化与ｓＩＬ－２Ｒ水平密切相关，ＧＣ可通过影响ＩＬ－２活性及ｓＩＬ－２Ｒ水平而发挥免疫治疗作用。     

老年急性脑血管病并多器官功能衰竭患者SIL-2R和T细胞亚群的测定

采用ＥＬＩＳＡ和ＡＰＡＡＰ法对３２例老年急性脑血管病（ＡＣＶＤ）并多器官功能衰竭（ＭＯＦ）患者及４０例老年和３５例非老年ＡＣＶＤ患者血清可溶性白细胞介素２受体（ＳＩＬ２Ｒ）及Ｔ细胞亚群水平进行了测定。并与３０例对照组比较。结果显示，疾病各组除ＣＤ３外ＳＩＬ２Ｒ和ＣＤ８均较对照组明显升高，ＣＤ４／ＣＤ８比值则明显下降，其中以老年ＡＣＶＤ并ＭＯＦ组变化最为显著，与老年和非老年ＡＣＶＤ组比较，亦有显著性差异；ＣＤ４水平老年ＡＣＶＤ并ＭＯＦ组较老年和非老年ＡＣＶＤ组及对照组明显降低，老年和非老年ＡＣＶＤ组与对照组比较无显著性差异；上述指标也与老年ＡＣＶＤ并ＭＯＦ患者的预后密切相关     

Neuroleptic treatment increases soluble IL-2 receptors and decreases soluble IL-6 receptors in schizophrenia

The cytokines interleukin-2 (IL-2) and interleukin-6 (IL-6) increase during immune activation, they are released from activated astrocytes and microglial cells in the central nervous system (CNS), and they are able to enhance the catecholaminergic neurotransmission. This study focused on the soluble receptors of IL-2 and IL-6 (sIL-2R, sIL-6R) as a part of the regulation system of IL-2 and IL-6. We studied serum levels of sIL-2R in 30 schizophrenic patients not under neuroleptic medication during an acute exacerbation of the disease and reexamined these patients under neuroleptic treatment after clinical improvement. The SIL-6R levels of 39 schizophrenic patients were estimated under the same conditions. The results were compared with the levels of sIL-2R and sIL-6R in 42 healthy controls. No difference was found between the schizophrenic patients before neuroleptic treatment and the healthy controls. During neuroleptic treatment, however, there was a significant increase of sIL-2R levels and a significant decrease of the sIL-6R levels between the pre- and post-conditions. In comparison with healthy controls, the treatment group also showed increased sIL-2R levels and decreased sIL-6R levels. These results suggest that treatment with neuroleptics is associated with increased sIL-2R and decreased sIL-6R. Since sIL-2R bind and inactivate IL-2, whereas sIL-6R form an active complex with IL-6, the increase of sIL-2R and the decrease of sIL-6R together may reflect a functional down regulation of these activating cytokines. This suggests that neuroleptic therapy has a differentiated immunomodulatory effect.     

黄芪穴位注射对慢性精神分裂症血可溶性白细胞介素2受体的影响

目的:探讨足三里穴位注射黄芪液对慢性精神分裂症患者免疫功能的影响。方法:对30例患者足三里穴位注射黄芪液,分别于注射前、注射4周和8周用酶联免疫法检测血可溶性白细胞介素2受体(sIL-2R)变化,并与30例健康者比较,进行相关因素分析。结果:穴位注射前患者sIL-2R水平显著高于健康者,注射后显著降低;老年组的sIL-2R水平明显高于青年组及中年组;氯丙嗪组sIL-2R水平明显高于氯氮平组及联合用药组;不同临床亚型组间的sIL-2R水平无显著差异。结论:足三里穴位注射黄芪液对慢性精神分裂症患者异常偏高的sIL-2R有显著改善作用。     

Relationship between platelet activation and cytokines in systemic inflammatory response syndrome patients with hematological malignancies.

We investigated the significance of platelet activation and platelet-derived microparticles (PMP) in 14 patients with systemic inflammatory response syndrome (SIRS) and hematological malignancies. In the phenotypic analysis of lymphocytes, there was a significant decrease of total and activated T cells after panipenem/betamipron (PAPM/BP) treatment (p<0.05). The percentages of helper/inducer T cells and suppressor/cytotoxic T cells were insignificantly decreased after PAPM/BP treatment. The number of natural killer (NK) cells of potent activity was significantly decreased after treatment (p<0.05). The levels of the cytokines interleukin (IL)-1beta, IL-6, and IL-8 in the patients were increased before treatment. IL-1beta concentrations were not changed after treatment. In contrast, the IL-6 and IL-8 levels were significantly decreased (p<0.05) after treatment, while tumor necrosis factor (TNF)-alpha and interferon gamma remained almost normal. We found an increase of soluble IL-2 receptor (sIL-2R) and soluble vascular cell adhesion molecule-1 (sVCAM-1) levels in the patients before treatment. After treatment, the sIL-2R concentrations tended to be decreased and sVCAM-1 levels showed a significant decrease (p<0.01). In contrast, soluble thrombomodulin (sTM) level did not change. Regarding the platelet activation markers, CD62P, CD63, and PMP levels in the patients were increased before treatment. CD62P and CD63 tended to be decreased after treatment, whereas PMP levels were significantly reduced from 1,056+/-103 to 762+/-64/10(4) platelets (p<0.05). Furthermore, CD62P, CD63, and PMP correlated with the levels of IL-6 and IL-8. These results suggest that activated platelets and PMP may be predictive markers in pre-disseminated intravascular coagulation and hypercytokine conditions related to SIRS.     

Immune disturbances during major depression: upregulated expression of interleukin-2 receptors

We determined the following immune parameters in drug-free, major depressed patients and in age- and sex-matched healthy controls: the number and percentage of interleukin-2 receptor (IL-2R) bearing cells (CD25+, anti-TAC), serum circulating levels of soluble (s)IL-2Rs, the pre- and postdexamethasone phytohemagglutinin (PHA)-induced accumulation of sIL-2Rs in culture supernatant, and the number of T helper (CD4+) and T suppressor (CD8+) cells. In comparison with normal volunteers, patients with major depression had a higher number and percentage of CD25+ cells, higher concentrations of serum circulating sIL-2Rs, higher supernatant sIL-2Rs after stimulation with PHA, and a higher number of CD4+ cells. The CD4+/CD8+ ratio and the number of CD4+ cells were significantly and positively related to the number of cells expressing the CD25+ antigen. These results may indicate that depressed patients display an increased number of T cells in an early phase of activation.