白细胞介素与重症肌无力

重症肌无力(MG)是选择性侵犯神经肌肉接头处突触后膜上乙酰胆碱受体(AchR)的自身免疫性疾病。乙酰胆碱受体抗体(AchRab)介导的体液免疫和T细胞介导细胞免疫是其主要发病机制,但其免疫紊乱的具体环节尚不清楚。自细胞介素(IL)作为细胞因子的重要组成部分,其活性的改变可反映体内免疫功能紊乱的状况;可直接影响B细胞的数量和功能,进而影响AchRab的产生。本文着重介绍相关IL在MG中的作用及有关机制。     

重症肌无力患者外周血干扰素—γ和白细胞介素—10分泌性T细？…

目的 探讨重症肌无力（ＭＧ）患者乙酰胆碱受体（ＡＣｈＲ）特异性Ｔ细胞免疫应答及其国酰胆碱受体抗体间的关系。及该类Ｔ细胞在胸腺瘤切除前后的变化。方法 采用酶联免疫斑点技术在１５例ＭＧ患者和１０例其他神经疾病（ＯＮＤ）患者中,检测在ＡＣｈＲ等不同抗原特异干扰素－γ分泌性Ｔｈ１细胞和白细胞介素－１０（ＩＬ－１０）分泌笥ＺＴｈ２细胞数。结果 ＡＣｈＲＡｂ阳性组ＭＧ患者外周血ＡＣｈＲ特异性ＩＦＮ－γ、ＩＬ＿     

白细胞介素—6在重症肌无力发病中的作用研究进展

重症肌无力 (MG)是主要累及神经肌肉接头 (NMJ)处突触后膜上乙酰胆碱受体 (Ach R)的全身性自身免疫性疾病。患者细胞和体液免疫应答均存在异常。白细胞介素 - 6(IL- 6 )是机体内复杂的细胞因子网络中必需成分之一 ,在免疫应答中发挥重要作用。它除了影响 B细胞和 T细胞增殖和分化外 ,还具有多种其它重要的生物学功能。现就 IL - 6与MG的研究进展作一综述 ,以阐明 IL - 6在 MG发病机理中的作用 ,探讨 MG新的免疫治疗方法。1　 IL- 6及其受体的生物学活性机体内多种淋巴和非淋巴组织细胞均能表达 IL- 6 ,如人体成纤维细胞、单核细胞…     

重症肌无力患者外周血单个核细胞白细胞介素6活性变化

探讨白细胞介素 6(IL -6)在重症肌无力 (MG)发病机理中的作用及其临床意义。　　方法　采用3H -TdR掺入法检测 40例正常对照及 42例MG患者外周血单个核细胞IL -6分泌活性。　　结果　MG患者组IL -6活性显著高于正常对照组 ,且IL -6活性变化与乙酰胆碱受体抗体产生以及与MG临床类型、病情、预后密切相关。　　结论　IL -6在MG发病机理中起着重要作用 ,检测IL -6活性对区分MG临床类型、判断病情、推测预后、指导治疗有重要的参考价值。     

AChRab阳性和阴性重症肌无力IL—4和IFN—γ分泌细胞的检测

胸腺切除术的MG患者,分成AChRab阳性和阴性两组。发现在阳性组中,其外周血和骨髓中IL-4和IFN-γ分泌细胞数量均高于AChRab阴性组,(P<0.05)。而胸腺中两组差异无显著性。AChRab阳性的MG病人IL-4分泌细胞和IFN-γ分泌细胞的水平异常增高显示IL-4和IFN-γ在MG自身抗体的产生中均有重要作用,T细胞的不同亚类都参与了MG的免疫调节。     

重症肌无力患者外周血乙酰胆碱受体特异性T细胞sIL—2R,IFN—γ,IL— …

目的 了解ＭＧ患者的乙酰胆碱受体（ＡＣｈＲ）特异性细胞免疫应答。方法 采用酶联免疫吸附试验（ＥＬＩＳＡ）检测３０例ＭＧ患者２０名健康对照者经ＡＣｈＲ刺激后外周血单核细胞（ＰＢＭＣ）辅助性Ｔ细胞１（Ｔｈ１）相关的干扰素（ＩＦＮ）－γ，辅助性Ｔ细胞（Ｔｈ２）相关的白细胞介素（ＩＬ）－４及与细胞免疫活化密切要关的可溶性白细胞介素－２受体（ｓＩＬ－２Ｒ）的分泌，用逆转录－聚合酶链反应（ＲＴ－ＰＣＲ）结合狭     

重症肌无力患者血清白细胞介素—6水平测定

目的探讨重症肌无力(MG)与白细胞介素-6(IL-6)的关系.方法采用双抗体夹心ELISA法对30例MG患者用糖皮质激素(GC)治疗前、治疗2个月后和22例正常对照血清IL-6、乙酰胆碱受体抗体(AchRab)水平进行检测.结果MG患者组血清IL-6水平显著高于对照组(P＜0.01),MG患者组血清IL-6水平在用GC治疗2个月后显著降低(P＜0.01),其血清IL-6与血清AchRab水平呈正相关(r=0.693,P＜0.01).结论IL-6与MG发病密切相关,IL-6参加了MG的免疫病理过程;检测血清IL-6水平对MG临床有重要价值;GC可抑制IL-6合成及AchRab产生.     

重症肌无力患者外周血白细胞糖皮质激素受体的检测

目的探讨重症肌无力患者外周血白细胞糖皮质激素受体含量与重症肌无力发病的关系.方法用放免法测定重症肌无力患者血浆糖皮质激素水平,用放射配体结合法测定其外周血白细胞糖皮质激素受体含量.结果测定前2个月未曾接受糖皮质激素治疗的患者,其白细胞糖皮质激素受体平均值为(6799±2055)位点/细胞,与对照组(2839±1787)位点/细胞相比,位点数明显增高(P＜0.001).与患者的性别、年龄及疾病的临床类型无关.重症肌无力患者血浆皮质醇浓度为(458±170) nmol/L,正常对照组为(413±156) nmol/L,二者无明显差异(P＞0.05).结论重症肌无力患者外周血白细胞糖皮质激素受体含量增多,可能与重症肌无力发病有关.     

Cellular localization and expression patterns of interleukin-10, interleukin-4, and their receptors in multiple sclerosis lesions

Cytokines have been shown to play a crucial role in the pathogenesis of multiple sclerosis (MS). However, still limited data are available on the expression of anti-inflammatory cytokines within the central nervous system (CNS) during MS lesion development. Therefore, we have examined the expression of the anti-inflammatory cytokines, interleukin-10 (IL-10) and IL-4, and their specific receptors, IL-10R and IL-4R, in postmortem human brain tissue obtained from MS patients. Specific patterns of protein localization and expression for both proteins could be observed within active and chronic MS lesions. Strongest IL-10 immunoreactivity was observed in reactive astrocytes within active demyelinating lesions and the hypercellular rim of chronic active MS lesions. Moreover, perivascular macrophages were immunoreactive for IL-10 in (chronic) active MS lesions. Most intense IL-4 immunoreactivity was detected in reactive fibrillary astrocytes within the hypocellular regions of chronic active and chronic inactive MS lesions. Strong immunoreactivity for IL-10R and IL-4R was detected on macrophages in both parenchymal and perivascular areas and on reactive astrocytes in active and chronic MS lesions. Our results indicate that IL-10 and IL-4 have an active role in CNS immune responses. The specific patterns of protein localization and protein expression for both IL-10 and IL-4 in MS lesions at different stages of development suggest that these anti-inflammatory cytokines and their receptors participate in processes leading to the formation of chronic MS lesions.     

精神分裂症患者血浆白介素6、10、12水平研究

目的　探讨白介素 (IL) 6、1 0、1 2在精神分裂症的病因与发病机制中的作用。方法　采用酶联免疫吸附法 (ELSIA)检测 57例精神分裂症和 2 9名健康对照的血浆IL 6、IL 1 0、IL 1 2水平。结果　精神分裂症患者组血浆IL 1 2水平明显高于对照组 (P <0 0 5) ,而IL 6、IL 1 0水平两组间无显著性差异 ;女性患者的血浆IL 1 0水平明显低于女性对照组 (P <0 0 5) ,其IL 1 2则高于对照组 (P <0 0 5) ;Ⅱ型精神分裂症患者的血浆IL 6水平明显高于Ⅰ型(P <0 0 5) ,家族性亚型患者的IL 6水平明显高于散发性亚型 (P <0 0 1 ) ;患者组IL 6与IL 1 0呈正相关 (P <0 0 0 1 )。结论　精神分裂症患者存在IL 1 2介导的免疫功能异常 ,血浆IL 6水平升高可能是其某些临床亚型的特征性免疫学指标之一 ,细胞因子间的相互关系在精神病理状态下可能发生改变     

白细胞介素2、白细胞介素10及人类白细胞抗原G与肝移植的急性排斥

背景：移植肝急性排斥反应是导致移植物功能损伤的主要危险因素,目前诊断主要靠肝组织穿刺活检,带来感染、出血等风险。如何无创、简单、准确地进行诊断成为当前该领域的热点。目的：观察分析白细胞介素2、白细胞介素10、人类白细胞抗原G的表达与人类肝移植急性排斥之间的关系。方法：用酶联免疫方法检测59例肝脏移植受者外周血白细胞介素2、白细胞介素10、人类白细胞抗原G的表达情况。将受者按照有无急性排斥反应分为急性排斥组和非排斥组;并将非排斥组按肝功能情况分为肝功能正常组与异常组。结果进行统计学分析,并绘制ROC曲线,比较曲线下面积及其临界值的敏感性和特异性。结果与结论：急性排斥组外周血中白细胞介素10、人类白细胞抗原G表达均低于与非排斥组(P=0.032, 0.002),而排斥组中白细胞介素2高于非排斥组(P=0.002)。肝功正常组与异常组间白细胞介素10、人类白细胞抗原G表达差异无显著性意义(P=0.525,0.084),而肝功能异常组白细胞介素2表达高于肝功能正常组(P=0.02)。ROC曲线下面积为人类白细胞抗原G >白细胞介素2>白细胞介素10。结果提示,白细胞介素2、白细胞介素10、人类白细胞抗原G的表达都与排斥相关,三者中人类白细胞抗原G为诊断急性排斥的最佳指标。     

文拉法辛对单相抑郁患者IL-10和IL-4水平的影响

目的观察单相抑郁患者白介素10(IL-10)、白介素4(IL-4)水平及文拉法辛对单相抑郁患者IL-10和IL-4水平的影响,探讨IL-10、IL-4水平与单相抑郁的关系及文拉法辛的抗抑郁机制。方法选取2016年6月-2017年12月于天津市安定医院就诊的符合《国际疾病分类(第10版)》(ICD-10)诊断标准的单相抑郁住院患者80例为病例组,给予文拉法辛治疗8周。同期选取天津市安定医院的健康体检者82例为对照组。于治疗前和治疗8周后采用酶联免疫吸附试验(ELISA)检测病例组IL-10、IL-4水平并用汉密尔顿抑郁量表24项版(HAMD-24)评定疗效,于入组时用ELISA检测对照组IL-10、IL-4水平。结果治疗前,病例组IL-10、IL-4水平均低于对照组,差异均有统计学意义(P均0. 05)。治疗8周后,病例组IL-10、IL-4水平均高于治疗前,差异均有统计学意义(P均0. 05);病例组与对照组IL-10、IL-4水平差异无统计学意义(P均 0. 05)。治疗8周后,病例组HAMD-24总评分及焦虑/躯体化、迟缓、绝望感因子评分均低于治疗前,差异均有统计学意义(P均0. 05)。病例组治疗前的IL-10、IL-4水平与HAMD-24评分呈负相关(r=-0. 772、-0. 654,P均0. 05)。结论单相抑郁的发生可能与IL-10、IL-4水平降低相关,文拉法辛可改善单相抑郁患者的症状,其可能是通过调节IL-10、IL-4水平发挥抗抑郁作用。     

白介素-6、10、12与精神分裂症临床特征的关系

目的 检测精神分裂症患者血浆IL-6、IL-10和IL-12水平,探讨其与精神分裂症临床特征的关系。方法 对57例精神分裂症患者和29例健康人,采用酶联免疫吸附法(ELSIA)检测其血浆IL-6、IL-10、IL-12水平,采用阳性和阴性症状评定量表(PANSS)评定患者的症状特征。结果 患者组血浆IL-12水平高于正常对照组(P<0.05),且与疾病的严重程度皇正相关;阴性症状组患者IL-6水平明显高于阳性症状组和正常对照组,而其IL-10水平则低于阳性症状组;急性或亚急性起病者血浆IL-10水平明显低于慢性起病组。 结论 精神分裂症存在细胞免疫异常,IL-12在精神分裂症的发病机制中起一定作用,IL-6和IL-10则与其部分临床特征有关。     

Opposite role of alpha2- and beta-adrenoceptors in the modulation of interleukin-10 production in endotoxaemic mice

Our aim was to investigate the role of adrenoceptors in the modulation of in vivo interleukin-10 (IL-10) production in lipopolysaccharide (LPS)-treated mice. The effect of different adrenergic drugs on plasma concentration of IL-10 was measured by ELISA 90 min after LPS injection. Our results confirmed the involvement of beta-adrenoceptors since the beta-agonist isoproterenol significantly increased the IL-10 production in response to LPS stimulation, whereas the beta-antagonists propranolol decreased it. In contrast, the alpha2-agonists UK-14304, clonidine and xylazine significantly decreased the IL-10 plasma level, whereas the alpha2-antagonists CH-38083, prazosine and WB-4101 increased it. Our results provide the first in vivo evidence that, in addition to beta-adrenoceptors; alpha-adrenoceptors play also a very important role in the regulation of IL-10 production under endotoxaemic conditions.     

Circulating interleukin-10 and interleukin-12 in Parkinson's disease

Background – Interleukin (IL)‐12 is a heterodimeric cytokine produced by activated blood monocytes, macrophages and glial cells. It enhances differentiation and proliferation of T cells and increases production of proinflammatory cytokines. IL‐10 is a pleiotropic cytokine produced by both lymphocytes and mononuclear phagocytes including microglia. Recent studies demonstrated the neuroprotective effect of IL‐10. There is little information about the involvement of IL‐12 or IL‐10 in the pathophysiology of Parkinson’s disease (PD). Objectives – The objective of our study was to assess the role of IL‐12 as a potential marker of immune reactions in patients with PD and to investigate whether IL‐10, an immunosuppressive cytokine, may have a neuroprotective effect in the pathogenesis of PD. Patients and methods – We measured using immunoassay serum IL‐12 and IL‐10 levels in 41 patients with PD in comparison with serum levels in 19 healthy subjects (controls) age and sex matched. IL‐12 and IL‐10 levels were tested for correlation with sex, age, disease duration, Hoehn and Yahr stage and the UPDRS III score. Results – The PD group presented with significantly increased IL‐10 levels when compared with the control group (P = 0.02). The increase observed was not affected by the treatment status. A strong and significant correlation between IL‐10 and IL‐12 levels was observed in patients with PD (R_S = 0.7, P < 0.000001). Conclusions – Our findings suggest that IL‐10 may be involved in the pathogenetic mechanisms of PD. The elevation of IL‐10 and the significant correlation between IL‐10 and IL‐12, a proinflammatory cytokine, may suggest that immunological disturbances and neuroprotective mechanisms are involved in patients with PD.     

Interleukin-4, interleukin-10, and interleukin-1-receptor antagonist but not transforming growth factor-beta induce ramification and reduce adhesion molecule expression of rat microglial cells

The activity of microglial cells is strictly controlled in order to maintain central nervous system (CNS) immune privilege. We hypothesized that several immunomodulatory factors present in the CNS parenchyma, i.e., the Th2-derived cytokines interleukin (IL)-4 and IL-10, interleukin-1-receptor-antagonist (IL-1-ra), or transforming growth factor (TGF)-beta can modulate microglial morphology and functions. Microglial cells were incubated with IL-4, IL-10, IL-1-ra, TGF-beta, or with astrocyte conditioned media (ACM) and were analyzed for morphological changes, expression of intercellular adhesion molecule (ICAM)-1, and secretion of IL-1beta or tumor necrosis factor (TNF)-alpha. Whereas untreated controls showed an amoeboid morphology both Th2-derived cytokines, IL-1-ra, and ACM induced a morphological transformation to the ramified phenotype. In contrast, TGF-beta-treated microglial cells showed an amoeboid morphology. Even combined with the neutralizing antibodies against IL-4, IL-10, or TGF-beta ACM induced microglial ramification. Furthermore, ACM did not contain relevant amounts of IL-4 and IL-10, as measured by enzyme-linked immunosorbent assay (ELISA). Flow cytometry showed that lipopolysaccharide (LPS)-induced ICAM-1-expression on microglial cells was strongly suppressed by ACM, significantly modulated by IL-4, IL-10, or IL-1-ra, but not influenced by TGF-beta. The LPS-induced secretion of IL-1beta and TNF-alpha was only reduced after application of ACM, whereas IL-4 or IL-10 did not inhibit IL-1beta- or TNF-alpha secretion. TGF-beta enhanced IL-1beta- but not TNF-alpha secretion. In summary, we demonstrate that IL-4, IL-10, and IL-1-ra induce microglial ramification and reduce ICAM-1-expression, whereas the secretion of proinflammatory cytokines is not prevented. TGF-beta has no modulating effects. Importantly, unidentified astrocytic factors that are not identical with IL-4, IL-10, or TGF-beta possess strong immunomodulatory properties.     

Circulating levels of interleukin-17A,tumor necrosis factor-alpha,interleukin-18, interleukin-10, and cognitive performance of patients with relapsing-remitting multiple sclerosis

Multiple sclerosis (MS) is associated with cytokine imbalance and high rate (40–70%) of cognitive impairment.

The objective of this study is to investigate the relationship between serum concentrations of tumor necrosis factor (TNF)-alpha, interleukin (IL)-17A, IL-18, IL-10, and cognitive performance in patients with relapsing-remitting MS (RRMS).

Methods

The study comprised 159 patients with RRMS (mean age 40.08 ± 8.48 years) in remission phase and 86 age-, gender-, and education-matched healthy controls. Paced Auditory Serial Addition Test (PASAT), Symbol Digit Modalities test (SDMT), and Isaacs test were used for assessment of working memory, attention, visuo-perceptual abilities, information processing speed, and executive functions. Serum cytokine concentrations were measured by enzyme-linked immunosorbent assay (ELISA).