抑郁症首次发病维吾尔族、汉族患者血清白介素-2、6及其可溶性受体水平的对照研究

目的:探讨抑郁症首次发病的维吾尔族(维族)、汉族患者血清白介素(IL)-2、IL-6及其可溶性受体(sIL-2R、sIL-6R)水平的变化。方法:对117例首次发病的抑郁症患者(抑郁症组,维族亚组57例,汉族亚组60例)给予文拉法辛治疗4周。治疗前后采用汉密尔顿抑郁量表(HAMD)-17项评定病情,采用酶联免疫吸附法(ELISA)检测血清IL-2、IL-6及sIL-2R、sIL-6R水平;并与性别、年龄相匹配的正常对照组(维族、汉族各55例)比较。结果:抑郁症维族及汉族亚组HAMD评分治疗后较治疗前显著下降(P均0.01),两亚组间差异无统计学意义。抑郁症组治疗前血清IL-2、IL-6及sIL-2R、sIL-6R水平明显高于正常对照组(P均0.01),且IL-2、sIL-6R水平在维族与汉族亚组间差异有统计学意义(P均0.01);治疗后血清IL-2、IL-6及sIL-2R、sIL-6R水平较治疗前明显下降(P均0.01)。结论:维族和汉族抑郁症患者均有免疫失调;文拉法辛治疗能改善抑郁症病情及免疫失调。     

老年与中青年脑梗死患者淋巴细胞亚群的对比研究

目的探讨不同年龄阶段脑梗死患者与淋巴细胞亚群的关系。方法选择101例临床确诊的急性脑梗死(ACI)患者,分成老年ACI组(66例)和中青年ACI组(35例)。选择对照组50例,应用流式细胞分析仪检测ACI患者和对照组外周血中淋巴细胞亚群相对计数。结果①老年脑梗死患者与正常对照组比较:CD8+T和CD19+B细胞百分率升高差异有统计学意义(P<0.05);CD4/CD8和CD4+T细胞百分率降低差异有统计学意义(P<0.05);CD3+T细胞百分率变化不明显(P>0.05)。②中青年脑梗死患者与正常对照组相比较:CD4+T细胞百分率和CD4/CD8降低差异有统计学意义(P<0.05);而CD3+T、CD8+T和CD19+B细胞百分率变化不明显(P>0.05)。③老年ACI组患者与中青年ACI组患者比较:CD8+T和CD19+B细胞百分率升高差异有统计学意义(P<0.05);CD3+T、CD4+T细胞百分率和CD4/CD8比较变化不明显(P>0.05)。结论 ACI患者体内淋巴细胞亚群发生重新分布,尤其老年ACI淋巴细胞亚群变化显著,这为我们在临床治疗中提供了新的思路。     

脑卒中后抑郁患者血清白细胞介素-6水平变化的研究

目的研究脑卒中后抑郁(PSD)患者血清白细胞介素-6(IL-6)水平变化,探讨PSD患者的抑郁与免疫功能变化的关系。方法采用放射免疫法检测59例PSD患者、36例非PSD患者及43例正常人的血清IL-6水平。59例PSD患者随机给予抗抑郁治疗 脑血管病恢复期方案治疗(n=29)或仅给予脑血管病恢复期方案治疗(n=30),观察患者治疗前后血清IL-6水平变化。结果治疗前,PSD组血清IL-6水平显著高于非PSD组(P<0.01)和正常对照组(P<0.01);治疗后,PSD抗抑郁治疗组与PSD未抗抑郁治疗组相比,HAMD评分(P<0.01)和IL-6水平(P<0.01)均显著降低。在PSD组治疗前、PSD抗抑郁治疗组及PSD未抗抑郁治疗组治疗后,HAMD评分与血清IL-6水平相关系数分别为0.375(P<0.01)、0.452(P<0.01)和0.397(P<0.01)呈显著性正相关。结论PSD患者血清IL-6水平明显升高并且与抑郁程度相关。     

加巴喷丁治疗糖尿病周围神经痛患者的临床疗效及对血清TNF-α、IL-6的影响

目的通过观察加巴喷丁(GBP)对糖尿病周围神经痛(DPN)患者的疗效以及血清肿瘤坏死因子(TNF-α)、白介素-6(IL-6)的影响。方法 47例DPN患者按是否服用GBP随机分为GBP组24例与DPN对照组23例,糖尿病无神经痛患者25例为糖尿病(DM)组,成年健康体检者25例为正常对照(NC)组。观察DPN患者治疗前、治疗1、2、4 w后的视觉模拟评分(VAS)分值变化以及药物副作用。ELISA法测定血清中TNF-α、IL-6的水平。结果治疗前GBP组与DPN对照组VAS比较,差异无统计学意义(P>0.05);GBP组治疗后1、2、4 w VAS分值均显著下降,与治疗前及同期DPN对照组比较,差异有统计学意义(P<0.01);DPN对照组各时期VAS分值差异无统计学意义(P>0.05)。DM、DPN各组血清TNF-α、IL-6均高于NC组,差异有统计学意义(P<0.01),DPN组血清TNF-α、IL-6又高于DM组,差异有统计学意义(P<0.01,P<0.05);与治疗前比较,GBP组治疗后血清TNF-α、IL-6水平下降,差异有统计学意义(P<0.01,P<0.05),DPN对照组治疗前后血清TNF-α、IL-6水平无明显变化,差异无统计学意义(P>0.05)。治疗过程中有1例出现嗜睡,3例出现眩晕,但均可耐受,观察期间血常规、肝肾功能无明显变化。结论加巴喷丁治疗糖尿病神经痛效果确切,副作用轻微,可降低机体血清TNF-α和IL-6水平。     

高频重复经颅磁刺激辅助治疗脑卒中后抑郁症疗效观察

目的探讨高频重复经颅磁刺激(rTMS)对脑卒中后抑郁症(PSD)的作用。方法将114例PSD患者随机分为联合治疗组38例(高频rTMS+氟西汀治疗)、抗抑郁药组38例(氟西汀治疗)和对照组38例(假刺激治疗),每周5次,共治疗8周。治疗前及治疗第4周、8周末采用汉密尔顿抑郁量表(HAMD)进行抑郁程度的评定。结果 3组治疗前HAMD评分差异无统计学意义(P0.05);治疗第4周末及8周末,联合治疗组、抗抑郁药组HAMD分值显著低于对照组,尤其联合治疗组(P0.05);治疗后第4周末,联合治疗组HAMD评分下降幅度较抗抑郁药组明显(P0.05)。结论高频rTMS辅助治疗PSD安全有效,高频rTMS结合抗抑郁药物治疗对PSD患者抑郁症状改善起效更快。     

肝豆状核变性T淋巴细胞亚群及NK细胞的变化

目的 研究肝豆状核变性(Wilson病,WD)患者的T淋巴细胞亚群及NK细胞亚群变化,并探讨其临床意义.方法 应用流式细胞仪直接免疫荧光染色法测定49例WD患者外周血T淋巴细胞亚群及NK细胞亚群,并与健康人组进行对照,同时对不同Child-Pugh分级患者的T细胞亚群及NK细胞进行比较分析.结果 WD组CD3+、CD4+、CD8+、CD4+/CD8+较对照组水平无明显变化,NK水平较对照组降低(P<0.05);病情重者CD3+、CD4+、CD4+/CD8+水平仍无差异,随病情加重NK水平显著降低(P<0.01).结论 WD存在NK细胞免疫失调,而T淋巴细胞免疫功能正常,病情重的患者NK细胞免疫功能更低.     

卒中相关性肺炎血清炎症因子和外周血淋巴细胞亚群的分析

目的 探讨卒中相关性肺炎（SAP）病人血清炎症因子白细胞介素（IL）-1β、IL-6、IL-4、肿瘤坏死因子-α（TNF-α）的水平变化及其临床意义。方法 选取2016年3月至2017年3月收治的48例SAP,根据A2D2S2L评分分为低危（0~2分,14例）、中危（3~9分,15例）、高危（≥10分,19例）三组。入院后次日清晨取空腹静脉血,应用流式细胞仪测定外周血T淋巴细胞亚群（CD3+、CD4+、CD8+）,应用酶联免疫吸附试验法检测血清炎症因子（IL-1β、IL-6、TNF-α、IL-4）。结果 随着危险程度的增高,血清IL-1β、IL-6、IL-4、TNF-α水平均明显增高（P<0.05）,外周血CD3+和CD4+细胞百分比显著增高（P<0.05）。低危组CD4+/CD8+显著高于高危组和中危组（P<0.05）,而后两组无统计学差异（P>0.05）;三组CD3+/CD8+均无显著差异（P>0.05）。结论 血清炎症因子IL-1β、IL-6、TNF-α、IL-4以及T细胞淋巴亚群变化情况反映SAP病人的A2D2S2L评分,血清IL-1β、IL-4、IL-6、TNF-α与A2D2S2L评分呈正相关,T细胞亚群CD3+、CD4+百分比与A2D2S2L评分呈负相关。     

雌二醇对实验性自身免疫性脑脊髓炎调节性T细胞及细胞因子的影响

目的 探讨雌二醇(E2)对实验性自身免疫性脑脊髓炎(EAE)大鼠调节性T细胞及细胞因子的影响.方法 将大鼠随机分为E2干预组和EAE对照组,记录其临床评分, 测定外周血CD4+CD25+、CD4+CD25+Foxp3+ T细胞水平以及TNF-α、IL-12表达水平,并观察腰膨大处炎细胞浸润情况.结果 (1)E2干预组发病率仅为30% ,低于EAE对照组(100%), 且发病高峰延迟;临床评分E2干预组[(1.8±1.3)分]比EAE对照组[(3.4±0.5)分]低, 差异有统计学意义(P<0.05);(2)E2干预组CD4+CD25+/CD4+ T细胞比值 (5.6±0.9)、CD4+CD25+Foxp3+/CD4+CD25+ T细胞比值(9.3±1.0)均高于EAE对照组[分别为(4.4±0.9)与(7.6±0.8)], 差异有统计学意义(均P<0.05);(3)血管"套袖"样改变EAE对照组较E2干预组明显;(4)E2干预组TNF-α及IL-12表达明显低于EAE对照组, 差异有统计学意义(均P<0.05).结论 E2可能通过改变调节性T细胞比例及细胞因子表达参与EAE免疫调节过程, 推测EAE临床症状缓解可能也与此机制相关.     

抑郁症自杀未遂患者若干生物学改变

目的:探讨抑郁症自杀未遂患者外周血中CD4+CD25+调节性T(Tr)细胞、白细胞介素2(IL-2)及IL-6水平与自杀行为间的关系。方法:患者组为44例抑郁症自杀未遂患者,对照组为30名健康正常者。患者组用选择性5-羟色胺再摄取抑制剂或文拉法辛治疗。治疗前后检测CD4+CD25+Tr、IL-2及IL-6。采用自杀未遂调查表评定两组严重程度。结果:患者组治疗前外周血中CD4+CD25+Tr、IL-2及IL-6均显著高于对照组(P<0.05或P<0.01)。患者组治疗后外周血中CD4+CD25+Tr、IL-2显著降低(P<0.01),IL-6变化不明显。两组比较差异无统计学意义(P>0.05)。患者病情严重程度与血中CD4+CD25+Tr、IL-2、IL-6水平均无显著相关。结论:抑郁症自杀未遂患者处于免疫紊乱状态,CD4+CD25+Tr、IL-2、IL-6与自杀行为间存在一定的关系。     

转染白介素12的神经干细胞免疫基因治疗大鼠C6恶性胶质瘤

目的本文对转染白介素12(IL-12)的神经干细胞用于免疫基因治疗大鼠颅内胶质瘤进行研究。方法运用脂质体法将质粒pcDNA3.1-scIL12转染到胎儿海马神经干细胞(hNSCs),通过RT-PCR方法进行转染细胞鉴定。将干细胞和C6细胞经立体定向方法注入大鼠颅内,并使用脑核磁和免疫组化方法观察肿瘤的生长情况。结果共同注射组及延期注射组生存期得到明显延长。通过MR动态观察我们发现,最初增大的肿瘤逐渐缩小至消失。经免疫组化染色发现这些浸润细胞多数为CD4( )、CD8( )的T细胞,并且CD8( )T淋巴细胞多于CD4( )细胞。结论表达IL-12的NSCs有很强的抗肿瘤效果,神经干细胞是基因治疗的良好载体。     

IL-32在神经胶质瘤中的表达及调节机制研究

目的 探讨白细胞介素(IL)-32在神经胶质瘤中的表达及调节机制. 方法 RT-PCR、Western blotting检测体外培养3d的神经胶质瘤细胞株CHG-5、U251 IL-32 mRNA和蛋白的表达;应用10 ng/mL IL-1β、IL-4、IL-6、IL-10、IL-17、肿瘤坏死因子(TNF)-α、TNF-β、干扰素(IFN)-γ作用U251细胞24 h后RT-PCR检测细胞IL-32 mRNA表达的变化;RT-PCR检测不同浓度IL-1β、TNF-α、IFN-γ作用U251细胞不同时间后IL-32 mRNA表达的变化. 结果 U251细胞IL-32 mRNA表达水平高于CHG-5细胞,IL-32蛋白表达水平(0.95±0.42)高于CHG-5细胞(0.28±0.13),差异均有统计学意义(P＜0.05); IL-1β、TNF-α、IFN-γ作用U251细胞24 h后IL-32 mRNA表达量增加,差异有统计学意义(P＜0.05),且IL-32 mRNA的表达量对IL-1β、TNF-α、IFN-γ刺激的浓度和时间有依赖性. 结论 IL-32在神经胶质瘤中高表达,IL-1β、TNF-α、IFN-γ对IL-32 mRNA的表达具有调节作用,且存在时间与剂量依赖性.     

Cognitive function in young and adult IL (interleukin)-6 deficient mice

Interleukin-6 (IL-6) is a cytokine shown to affect brain function and to be involved in pathological neurodegenerative disorders such as Alzheimer's disease (AD). In the present study we investigated the cognitive function in transgenic mice not expressing IL-6 (IL-6 KO) and in wild type (WT) genotype at 4 and 12 months of age, using a passive avoidance and an eight-arm radial maze tasks. Motor function was quantified using an Animex apparatus. Hippocampal choline acetyltransferase (ChAT) activity was evaluated in both genotypes. No difference was observed in both genotypes for spontaneous motor activity. The mean latency (s) to re-enter the shock box, was similar in both young mutant and WT mice. However, a decreased sensitivity (50%) to scopolamine (1 mg/kg) in mutant compared to WT mice, was obtained. IL-6 KO mice exhibited a facilitation of radial maze learning over 30 days, in terms of a lower number of working memory errors and a higher percentage of animals reaching the criterion as compared with WT genotype tested at both ages. Furthermore, mutant mice, at the age of 12 months, showed a faster acquisition (22 days versus 30 days to reach the criterion). The pattern of arm entry exhibited by IL-6 KO mice showed a robust tendency to enter an adjacent arm at both ages, while WT only at the age of 4 months. ChAT activity was inversely correlated with memory performance. These findings suggest a possible involvement of IL-6 on memory processes, even if the mechanism remains still unclear.     

Association of interleukin 6, interleukin 7 receptor alpha,and interleukin 12B gene polymorphisms with multiple sclerosis

Pro-inflammatory and anti-inflammatory cytokines have been shown to play a crucial role in the pathophysiology of multiple sclerosis (MS). We investigated the association between interleukin (IL) IL6-174 G/C (rs1800795), IL7RA C/T (rs6897932), and IL-12B A1188C (rs3212227) gene polymorphisms (SNPs) and MS. The study consisted of 297 unrelated MS patients and 135 healthy individuals. In IL6-174G/C (rs1800795), a significant association between the C allele and MS risk [OR 1.41, 95% CI (1.05–1.92); P?=?0.025] was found. Carriage of genotypes CC and CG were more common in MS patients [OR 1.58, 95% CI (1.04–2.39); P?=?0.031] and also in female MS patients [OR 1.68, 95% CI (1.02–2.79); P?=?0.043]. However, after applying Bonferroni’s correction the differences did not remain significant. No significant association between the IL7RA C/T (rs6897932) and IL12B A1188C (rs3212227) gene polymorphisms and MS susceptibility was observed. Regarding IL-12B A1188C (rs3212227), a significant association between the CC genotype and MS progression, expressed as MSSS, was demonstrated in the female MS group. Our results indicate that the distribution of IL6-174G/C (rs1800795) SNP was marginally associated with MS susceptibility. We also showed that IL-12B A1188C (rs3212227) can contribute to the progression of the disease in the Czech population.     

Negative affective responses to a speech task predict changes in interleukin (IL)-6

Laboratory studies show that individuals differ appreciably in the magnitude of their inflammatory responses to acute psychological stress. These individual differences are poorly understood, yet may contribute to variation in stress-associated disease vulnerability. The present study examined the possibility that affective responses to acute stress contribute to these differences. For this purpose, 102 relatively-healthy community volunteers (mean age 50 years; 60% female; 91.2% white) performed an acute stress protocol and measures of affective state and serum levels of the proinflammatory cytokine, interleukin (IL)-6 were collected at the end of a 30-min resting baseline, a 5-min evaluative public speaking task, and a 30-min recovery period. Results of regression analyses, controlling for age, race, gender, menopausal status, and body mass index, revealed a positive association of task-related increases in anger and anxiety with increases in IL-6 (R² change = .08, p = .004; R² change = .08, p = .005, respectively). Further examination showed that these affective responses to the task were independent predictors of change in IL-6. Cardiovascular reactivity to the task did not explain the association. These results suggest that individuals who exhibit angry or anxious responses to acute challenge are more vulnerable to stress-related increases in markers of systemic inflammation, possibly rendering them more susceptible to inflammatory disease.     

Bovine anterior pituitary progenitor cell line expresses interleukin (IL)-18 and IL-18 receptor

In the anterior pituitary gland, inflammatory mediators regulate cell function through an immuno-endocrine pathway. Recent studies have shown that undifferentiated stem cells act as immunomodulators. These studies prompted us to establish a progenitor cell line from the bovine anterior pituitary gland and to detail its function. First, we localised interleukin (IL)-18 by immunohistochemistry to the marginal cell layer of Rathke's pouch that is assumed to embody a stem/progenitor cell compartment of the postnatal pituitary gland. A cloned anterior pituitary-derived cell line from the bovine anterior pituitary gland was established from single cell clone by the limiting dilution method and was designated as bovine anterior pituitary-derived cell line (BAPC)-1. BAPC-1 cells constantly expressed mRNAs for IL-18 and IL-18 receptor, and grew steadily and rapidly in the medium containing epidermal growth factor and basic fibroblast growth factor. The cell line also expressed the mRNAs for the stem/progenitor cell- related factors such as Nanog, Oct-4, Ptch1, Nestin, Notch1, Hes1, Lrp and Fzd4, and the mRNAs for embryonic pituitary-related factors, such as Lhx3, PitX1 and Pit-1. The nuclei of BAPC-1 were immunostained positively for Pit-1, Hes1 and beta-catenin antibodies. Furthermore, BAPC-1 cells expressed mRNAs for cytokine such as IL-1alpha, IL-6, IL-7, IL-12 and IL-15. Stimulation of BAPC-1 cells with IL-18 increased expression of mRNAs for IL-1alpha, IL-6, IL-1beta and IL-8. At day 6 in culture, BAPC-1 cells also express growth hormone mRNA. These results strongly suggest that BAPC-1 is a stem/progenitor cell line and modulates the immuno-endocrine function of the anterior pituitary cells through its cytokine production.     

Multinucleated giant cell formation by microglia: induction by interleukin (IL)-4 and IL-13

To investigate the cellular origin and the mechanisms of multinucleated giant cell (MGC) formation in the CNS, various cytokines were applied to isolated murine microglia. All the single cytokines failed to induce MGC. However, interleukin (IL)-13 and IL-4 induced microglial MGC formation in the presence of colony stimulating factors, which was inhibited by either anti-IL-13 or anti-fms antibody. T helper 2 (Th2)-derived cytokines can induce MGC formation even in the absence of infectious agents.     

Production of tumor necrosis factor-alpha, interleukin 1-beta, interleukin 2, and interleukin 6 by rat leukocyte subpopulations after exposure to substance P

The interaction between components of the nervous system and multiple target cells in the cutaneous immune system has been receiving increasing attention. Recently, the involvement of neuropeptides has been demonstrated to play an important role in the inflammatory cascade. Neuropeptides such as Substance P are released by cutaneous neurons and modulate the function of immunocompetent and inflammatory cells as well as epithelial and endothelial cells. Substance P has been shown to function as a mediator for cell proliferation, cytokine production, and as an upregulator of various cell surface receptors. In this study, we show the effect of Substance P on the production of Tumor Necrosis Factor-alpha, Interleukin 1-beta, Interleukin 2, and Interleukin 6 by T-lymphocytes, macrophages and neutrophils. These data demonstrate that pathophysiological levels of Substance P induce production of cytokines in all three cell populations tested. Interestingly, T-cells demonstrated the highest percentage of cells expressing all four cytokines. In contrast, macrophages and neutrophils produced the highest absolute levels of cytokines. The elucidation of mediating mechanisms of Substance P activation of leukocytes is crucial to the understanding of the cutaneous inflammatory cascade and involvement of the peripheral nervous system on the immune system. These findings suggest that Substance P participates in the complex network of mediators that regulate cutaneous inflammation and potentially the rate of wound healing.     

Psychological stress-induced modulation of interleukin 2 receptor gene expression and interleukin 2 production in peripheral blood leukocytes

We explored the expression of the interleukin 2 receptor (IL-2R) and the synthesis of IL-2R messenger RNA by peripheral blood leukocytes obtained from medical students experiencing examination stress in three independent studies. The peripheral blood leukocytes obtained at low-stress baseline periods had significantly higher percentages of IL-2R-positive cells when compared with cells obtained from the same individuals during examinations. In addition, IL2-R messenger RNA in peripheral blood leukocytes decreased significantly during examination periods in a subset of 13 subjects. In one study, we found an increase in the accumulation of interleukin 2 in cultures of cells showing down regulation of IL-2R expression and IL-2R messenger RNA levels. While there are ample data demonstrating stress-associated decrements in the immune response in humans and animals, these data provide the first evidence that this interaction may be observed at the level of gene expression. The data suggest one mechanism whereby the central nervous system modulates the immune response during psychological stress.     

脑梗死患者血清脂联素、瘦素、CRP、IL-6与颈动脉内中膜厚度相关性研究

目的研究脑梗死患者血清脂联素、瘦素、炎性因子(C-反应蛋白,CRP;白介素-6,IL-6)与颈动脉内中膜厚度(IMT)的相关性,探讨血清脂联素、瘦素、CRP、IL-6在脑梗死发生发展过程中的作用。方法以96例脑梗死患者为梗死组,50例健康志愿者为正常对照组。用酶联免疫吸附法(ELISA)分别测定血清脂联素,瘦素及CRP、IL-6水平;测量IMT值,梗死组分为IMT<1.0 mm和IMT≥1.0 mm两亚组;同时梗死组进一步按脑梗死程度分为轻型、中型、重型亚组,用酶联免疫吸附法(ELISA)分别测定CRP、IL-6和血清脂联素、瘦素水平;分别测量颈动脉内中膜厚度(IMT)值。结果脑梗死组中,血清脂联素,瘦素及炎性因子含量分别与正常对照组相比较,差异具有统计学意义(p<0.05);脑梗死组中IMT≥1.0 mm者与IMT<1.0 mm者相比较,差异有统计学意义(p<0.05);脑梗死组中,随梗死程度变化,IMT与血清脂联素、瘦素、CRP、IL-6间,异有统计学意义(p<0.05),IMT与血清瘦素、CRP、IL-6呈明显正相关(r=0.52,p<0.01;r=0.48,p<0.01;r=0.50,p<0.01),脑梗死患者IMT与血清脂联素含量呈明显负相关(r=-0.848,p<0.01)。结论脑梗死患者IMT增厚,血清脂联素降低,瘦素、CRP、IL-6升高,脑梗死患者IMT与血清脂联素、瘦素、CRP、IL-6含量具有明显相关性。