抽动秽语综合征患者血清自身抗体与可溶性白介素-6受体表达

目的探讨抽动秽语综合征（TS）患者疾病过程中免疫损伤的相关机制。方法应用抗脑抗体（ABAb）、抗核抗体（ANA）、可溶性白介素-6受体（sIL-6R）及可溶性gp130（sgp130）的ELISA方法商品试剂盒,检测患者和正常人血清中sIL-6R、sgpl30及相应抗体的含量。结果TS组血清sIL-6R、sgp130含量显著高于正常对照组（44．078±15．777）：（30．290±9．048）,P〈0．01;（69．032±24．604）：（47．309±14．137）,P〈0．01）;TS患儿血清ABAb、ANA检出率显著高于对照组（66．7％：3．6％,P〈0．01;53．3％：25％,P〈0．05）。且ABAb水平与sgpl30负相关（r=-0．451,P=0．046）。结论在TS患者血清中sIL-6R、sgp130水平显著增高表明依赖IL-6信号传导的生理功能上调和反馈抑制的网络机制启动;自身免疫相关的损伤机制参与了疾病发生发展的病理生理过程。     

Decreased soluble interleukin-6 receptor in cerebrospinal fluid of patients with Alzheimer''s disease

The function of the cytokine interleukin-6 (IL-6) is augmented by soluble IL-6 receptors (sIL-6R). We investigated cerebrospinal fluid sIL-6R concentrations in patients with Alzheimer's disease (AD) compared to age-matched healthy subjects and individuals with at least one first degree relative with AD. We found a statistically significant decrease in sIL-6R levels in the AD group compared to controls. Complete analysis of the IL-6R complex seems crucial to better understand the impact of IL-6 in AD pathophysiology.     

Polymorphisms at the osteoprotegerin and interleukin-6 genes in relation to first-ever stroke

BACKGROUND: Arterial calcification and osteoporosis often coexist, especially in postmenopausal women. Osteoporosis associates with a substantially increased risk of stroke in elderly women, suggesting that impaired estrogen signaling may link stroke and osteoporosis. Osteoprotegerin (OPG, TNFRSF11B) and interleukin-6 (IL-6, IL6) are putative target genes for estrogen signaling and have been implicated in both cardiovascular diseases and osteoporosis. We hypothesized that specific polymorphisms in these genes may be associated with increased risk of ischemic stroke or intracerebral hemorrhage (ICH). METHODS: We performed a population-based prospective nested case-control study, in which the relationships between polymorphisms (OPG-1181G/C, OPG-950T/C and IL6-174G/C) and ischemic stroke and ICH were examined. Definitive first-ever stroke events (n = 388), i.e. ischemic stroke (n = 320), ICH (n = 61) and unspecified stroke (n = 7) cases, and controls without cardiovascular disease (n = 773), matched for age, sex and geographical region were studied. Univariate and multivariate models using conditional logistic regression, which included traditional risk factors, were used to test for association. RESULTS: Carriers of the OPG-1181C/C genotype had a significantly (p = 0.018) increased risk of ICH (OR, 2.69; 95% CI, 1.19-6.12) in the univariate analysis. After adjustments (hypertension, diabetes, BMI and triglycerides), this genotype remained significantly (p = 0.005) associated with ICH (OR, 6.04; 95% CI, 1.71-21.29). By contrast, no correlations were found between this genotype and ischemic stroke, nor between the OPG-950T/C or IL6-174G/C polymorphisms and stroke subtypes. CONCLUSIONS: In this population, the OPG-1181C/C genotype associates with first-ever ICH, implying that alterations in OPG-mediated signaling in the vasculature may be involved in the pathophysiology of this disease.     

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。     

Interleukin-6 and interleukin-1 receptor antagonist in acute stroke

Elevated plasma levels of interleukin-6 (IL-6), a key regulator of the acute phase response that includes increased fibrinogen synthesis, have recently been detected in patients with acute stroke. Nevertheless, the role of the acute phase response in stroke has been controversial, with some studies suggesting that preexisting infection accounts for most of the acute phase response. Increased IL-6 could signal the involvement of antiinflammatory activity, since IL-6 stimulates the production of endogenous antiinflammatory mediators such as interleukin-1 receptor antagonist (IL-1RA). To better understand the interaction of pro- and antiinflammatory acute phase processes in brain infarction, plasma levels of IL-1RA, IL-6, and acute phase proteins including fibrinogen and c-reactive protein (CRP) were measured within 4 ± 2 days of onset in 50 patients with acute ischemic stroke and in 20 age-matched healthy controls. After excluding patients with evidence of infection, both IL-1RA and IL-6 were significantly elevated in stoke patients compared with controls (p<0.0001). IL-1RA and IL-6 were both significantly correlated with levels of CRP, p<0.05 and p<0.001, respectively, but not with each other. Levels of IL-6 and IL-1RA, together with fibrinogen and CRP were higher in patients with infarcts of greater than 3 cm and lowest in patients with lacunar syndromes. Detection of increased peripheral levels of IL-1RA, IL-6, and additional acute phase reactants, including CRP, in acute stroke uncomplicated by infection suggests that an acute phase response to brain infarction occurs and that the magnitude of this response may be related to the volume of infarcted brain.     

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。     

Plasma concentrations of interleukin-1beta, interleukin-6, soluble interleukin-2 receptor and tumor necrosis factor alpha of depressed patients in Japan

There are a number of investigations which indicate the important relationship between depression and cytokines. In this study, we investigated plasma interleukin (IL)-1beta, IL-6, soluble IL-2 receptor (sIL-2R) and tumor necrosis factor (TNF)-alpha of depressed patients whose clinical evaluation was performed by the Hamilton Rating Scale for Depression (HAM-D) and the Profile of Mood States (POMS). They were compared with those of the control subjects, and before and after treatment with antidepressants. Before the treatment, plasma IL-1beta, IL-6, sIL-2R and TNF-alpha of the patients were not significantly different from those of the control subjects. sIL-2R was positively correlated with the POMS-tension-anxiety subscale and tended to have a positive correlation with HAM-D. After pharmacotherapy, TNF-alpha levels of the depressed patients increased, without any relationship between the change in the HAM-D or the POMS and the change in TNF-alpha. These results suggest that the plasma sIL-2R concentration is associated with mood state, and that the plasma TNF-alpha concentration is increased after pharmacotherapy in Japanese depressed patients.     

Serum soluble interleukin-2 receptor levels in chronic progressive, stable and steroid-treated multiple sclerosis

Serum levels of the soluble interleukin-2 receptor (sIL-2R), an indicator of T cell activation, were significantly elevated in chronic progressive MS (CPMS) patients, clinically stable MS patients and in patients with other neurological diseases (OND) as compared to healthy controls. Levels of sIL-2R in steroid treated CPMS patients were markedly lower than in untreated CPMS patients and were comparable to healthy controls. Thus, systemic T cell activation occurs in MS during clinically stable and progressive disease stages and in other neurological disorders. The ability of oral corticosteroids to depress serum sIL-2R levels in vivo may be one mechanism by which they exert their therapeutic effect.     

Elevated soluble interleukin-2 receptor levels in patients with active multiple sclerosis

The level of soluble interleukin-2 receptor (sIL-2R) was quantitated with enzyme-linked immunosorbent assay in serum and cerebrospinal fluid obtained from 24 patients with multiple sclerosis and 10 patients with other neurological disorders in whom immunological mechanisms are unlikely to participate. The sIL-2R level in the serum and cerebrospinal fluid of patients with multiple sclerosis in relapse was significantly higher compared with patients with multiple sclerosis in remission and with controls. The sIL-2R level, especially in the cerebrospinal fluid, showed higher sensitivity and specificity than other clinical parameters including the cerebrospinal fluid IgG ratio, peripheral lymphocyte CD4/CD8 ratio, cerebrospinal fluid myelin basic protein and oligoclonal bands. Our data suggest that measurement of the sIL-2R level may be useful in evaluating disease activity in patients with multiple sclerosis.     

Serum level of interleukin-6 in Chinese patients with multiple sclerosis

The aim of this study was to investigate the serum concentration of interleukin (IL)-6 in patients with relapsing-remitting MS (RR-MS), compare the difference between males and females, and explore the correlation between the serum concentration of IL-6 and clinical parameters like the current age, the age at onset, disease duration, disability (expanded disability status scale, EDSS), and the number of relapse. We compared the serum concentration of IL-6 in 39 patients with MS and 39 healthy controls matched with sex and age. The serum IL-6 concentration was measured by FlowCytomix. Compared to healthy controls, both the frequency of subjects with detectable level of IL-6 (P=0.005) and the serum concentration of IL-6 (P=0.004) were significantly higher in MS patients. When data were analyzed by gender, statistical significances between MS patients and healthy controls were observed only in females, although the frequency with detectable level and the serum concentration of IL-6 were higher in male MS patients than male controls. The serum level of IL-6 was found to be significantly positively correlated with the number of relapse for female MS patients (r(s)=0.511, P=0.009), with the current age for male MS patients (r(s)=0.700, P=0.005), and with the age at onset for all MS patients (r(s)=0.351, P=0.028). Our results may support that IL-6 is involved in the pathogenesis of MS and indicate that differences exist between male and female patients.     

Increased myelinating capacity of embryonic stem cell derived oligodendrocyte precursors after treatment by interleukin-6/soluble interleukin-6 receptor fusion protein

Neurosphere cells (NSc) derived from embryonic stem cells have characteristics of neural stem cells and can differentiate into oligodendrocyte precursors. Culture of NSc with IL6RIL6 chimera (soluble interleukin-6 receptor fused to interleukin-6) enhances their differentiation into oligodendrocytes with longer and more numerous branches and with peripheral accumulation of myelin basic protein (MBP) in myelin membranes indicating maturation. Gene expression profiling reveals that one of the proteins strongly induced by IL6RIL6 is a regulator of microtubule dynamics, stathmin-like 2 (SCG10/Stmn2), and gene silencing shows that Stmn2 plays an important role in the development of the mature oligodendrocyte morphology. IL6RIL6 acts as an effective stimulator of the myelinating function of ES cell-derived oligodendrocyte precursors, as observed upon transplantation of the IL6RIL6- pretreated cells into brain slices of MBP-deficient shiverer mice.     

Serum ferritin, transferrin and soluble transferrin receptor levels in multiple sclerosis patients

Over the last few years, increased evidence has supported the role of iron dysregulation in the pathogenesis of multiple sclerosis (MS), as iron is essential for myelin formation and oxidative phosphorylation. We studied indices of iron metabolism, such as serum iron, ferritin, transferrin and soluble transferrin receptor (sTFR) levels in 27 MS patients. Seven patients had chronic progressive active disease (CP-A), six had chronic progressive stable (CP-S), ten had relapsing remitting active (RR-A) and four had relapsing-remitting stable (RR-S) disease. sTFR levels were found to be significantly higher in CP-A (P = 0.021) and RR-A (P < 0.004) patients than in controls. sTFR levels were also elevated in CP-S patients but did not reach significance (P = 0.064). sTFR values in RR-S patients were comparable to those found in controls (P = 0.31). Ferritin levels were significantly elevated only in CP-A patients (P < 0.002). Patients of the CP group had significantly higher ferritin values than the RR patients (P < 0.004). Haemoglobin values as well as iron and transferrin levels were within normal limits in all patients. In conclusion, the increased serum sTFR and ferritin levels in nonanaemic MS patients with active disease reflect the increased iron turnover. The mild elevation of sTFR levels in CP-S patients may indicate active inflammation with ongoing oxidative damage that is not detectable by history or examination.     

Serum interleukin-6 is related to lower cognitive functioning in elderly patients with major depression*

Background: There is an increased evidence of an association between inflammatory mediators, particularly serum IL-6, depression and cognitive impairment in the elderly. This study aims at exploring the relation of peripheral IL-6 to cognitive functions in elderly patients with major depressive disorder (MDD).

Objectives: (1) Assessment of serum IL-6 levels and cognitive functions in elderly patients suffering from major depression and comparing them to healthy age-matched control subjects; (2) correlation between serum IL-6 levels and clinical characteristics of depression and cognitive functions in these patients.

Subjects and methods: The study is an observational, case-control study. It consisted of 80 subjects, 40 with the diagnosis of MDD according to the Diagnostic and Statistical Manual of Mental Disorders (DSM IV-TR) with early onset (first episode before the age of 60) and 40 community-dwelling subjects. They were subjected to the Structured Clinical Interview according to DSM-IV, Montreal Cognitive Assessment, Montgomery Asberg Depression Rating Scale, and serum IL-6 assay using ELISA.

Results: In the depression group, subjects had lower scores in cognitive testing, than the control group (p = 0.001). Serum IL-6 was found to have a negative correlation with cognitive testing in these patients even after controlling for the severity of depressive status and Body Mass Index (BMI) (p = 0.025).

Conclusions: MDD in elderly subjects is associated with decline in cognitive functions that may be related to peripheral IL-6 levels.     

A randomised phase II study of interleukin-1 receptor antagonist in acute stroke patients

OBJECTIVES: The cytokine interleukin (IL)-1 mediates ischaemic brain damage in rodents. The endogenous, highly selective, IL-1 receptor antagonist (IL-1ra) protects against ischaemic cerebral injury in a range of experimental settings, and IL-1ra causes a marked reduction of cell death when administered peripherally or at a delay in transient cerebral ischaemia. We report here the first randomised, double blind, placebo controlled trial of recombinant human IL-1ra (rhIL-1ra) in patients with acute stroke. METHODS: Patients within 6 hours of the onset of symptoms of acute stroke were randomised to rhIL-1ra or matching placebo. Test treatment was administered intravenously by a 100 mg loading dose over 60 seconds, followed by a 2 mg/kg/h infusion over 72 h. Adverse events and serious adverse events were recorded for up to 3 months, serial blood samples were collected for biological markers up to 3 months, and 5-7 day brain infarct volume was measured by computed tomography. RESULTS: No adverse events were attributed to study treatment among 34 patients randomised. Markers of biological activity, including neutrophil and total white cell counts, C reactive protein, and IL-6 concentrations, were lower in rhIL-1ra treated patients. Among patients with cortical infarcts, clinical outcomes at 3 months in the rhIL-1ra treated group were better than in placebo treated. CONCLUSIONS: These data suggest that rhIL-1ra is safe and well tolerated in acute stroke. In addition, rhIL-1ra exhibited biological activity that is relevant to the pathophysiology and clinical outcome of ischaemic stroke. Our findings identify rhIL-1ra as a potential new therapeutic agent for acute stroke.     

Serum levels of interleukin-33 and its soluble form receptor (sST2) are associated with cognitive performance in patients with schizophrenia

ObjectiveChanges in immune system have been reported in schizophrenia. This study aimed to evaluate the involvement of IL-33, a member of the IL-1 cytokine family, in schizophrenia and its association with cognitive performance in these patients.MethodsForty patients with chronic schizophrenia and 40 healthy subjects participated in the study. Serum levels of IL-33 and sST2 (soluble form of the IL-33 receptor) were measured using enzyme-linked immunosorbent assay (ELISA). Patients were evaluated with the Brief Assessment of Cognition in Schizophrenia (BACS) and the Schizophrenia Cognition Rating Scale (SCoRS).ResultsPatients with schizophrenia and controls presented similar serum levels of IL-33 and sST2. Levels of both markers were positively correlated with cognitive performance in patients with schizophrenia.ConclusionWe found a significant correlation between IL-33 and sST2 levels and cognition in schizophrenia. Our results might help in the understanding of how immune markers are associated with cognitive impairment in schizophrenia. It remains to be determined whether the association between IL-33/sST2 and cognition is restricted to patients with schizophrenia.     

卒中患者瘦素水平及瘦素受体基因多态性的实验研究

目的 探讨血清瘦素水平及瘦素受体基因多态性与卒中发病的关系. 方法 选择广州红十字会医院神经内科自2007年1月至2008年12月99例住院卒中患者[脑血管病(CVD)组]及97例同期住院的非卒中患者(对照组)做为研究对象,采用聚合酶链反应结合限制性片段长度多态性对2组患者进行瘦素受体基因Gln223Arg多态性进行检测,ELISA分析法检测血清瘦素水平. 结果 CVD组患者瘦素受体Gln223Arg的GG、GA、AA基因型分布频率分别为66.67%、20.20%、13.13%,与对照组的78.35%、15.46%、6.19%分布频率差异无统计学意义(P＞0.05);CVD组G和A等位基因频率分别为76.77%和25.23%,与对照组的86.08%和13.92%基因分布频率差异有统计学意义(P＜0.05).CVD组的血清瘦素水平明显高于对照组,差异有统计学意义(P＜0.05).非条件Logistic回归多因素分析表明高血压史、空腹血糖升高、TC升高、血清瘦素水平升高与卒中的发病相关. 结论 瘦素受体基因Gln223Arg的A等位基因、瘦素水平升高、高血压、空腹血糖升高、TC升高会增加卒中的发病风险.     

Serum immunoinhibitory factors in stroke patients

Immunoinhibitory factors in the sera of stroke patients were studied by an analysis of their capacity to influence the in vitro proliferative response of T cells. The evidence was obtained that the sera from stroke patients exhibited inhibitory activity on T cell proliferation. Although the nature of these inhibitory factors was not analyzed, it was clearly shown that their activity correlated with the degree of neurological defects, indicating that their determination may be of some prognostic value.