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。     

Ⅰ、Ⅱ型精神分裂症患者血浆相关细胞因子的对照研究

目的：探讨首发Ⅰ型(以阳性症状为主)、Ⅱ型(以阴性症状为主)精神分裂症患者血浆白细胞介素6(IL-6)、可溶性白细胞介素6受体(sIL-6R)及白细胞介素13(IL-13)水平的变化。方法：精神分裂症患者30例，其中Ⅰ型组17例，Ⅱ型组10例，混合型3例；健康对照者28名。采用酶联免疫吸附法(ELSLA)对血浆IL-6、sIL-6R及IL-13水平进行检测。结果：精神分裂症患者血浆IL-6及sIL-6R水平均显著高于对照组，而血浆IL-13水平显著低于对照组；Ⅱ型组患者的IL-6及sIL-6R水平均比Ⅰ型组高，其中Ⅱ型组患者IL-6显著高于Ⅰ型组，Ⅱ型组患者血浆IL-13水平显著低于Ⅰ型组；未发现患者组及对照组血浆IL-6、sIL-6R及IL-13之间的相关性。结论：Ⅰ、Ⅱ型精神分裂症患者均存在IL-6、IL-13水平异常，血浆IL-6水平升高、IL-13水平降低可能是Ⅱ型精神分裂症患者的特征性免疫学指标之一。     

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。     

首发精神分裂症和首发抑郁症患者血浆白细胞介素及其可溶性受体的对照研究

目的 在细胞因子水平探讨精神分裂症和抑郁症病理机制的异同.方法 首发精神分裂症和首发抑郁症患者各30例,分别单一接受利培酮(6 mg/d)、帕罗西汀(20 mg/d)治疗6周,治疗前后用阳性和阴性症状量表(PANSS)评估精神分裂症患者,并用汉密尔顿抑郁量表(HAMD)评估抑郁症患者.用酶联免疫吸附(ELISA)法测定治疗前后患者组和30名正常对照的血浆白细胞介素2(IL-2)、可溶性白细胞介素-2受体(slL-2R)、白细胞介素-6(IL-6)、可溶性白细胞介素-6受体(sIL-6R)的浓度.结果 ①治疗前,2个患者组的血浆IL-2、sIL-2R、IL-6、sIL-6R均高于正常对照组(P<0.05);精神分裂症组血浆sIL-2R高于抑郁症组(P<0.05),而IL-2、IL-6、sIL-6R低于抑郁症组(P<0.05).②治疗后,精神分裂症组血浆IL-2、sIL-6R较治疗前下降(P<0.05),抑郁症组血浆IL-2、sIL-2R、IL-6、sIL-6R均较治疗前下降(P<0.05);精神分裂症组血浆sIL-2R高于抑郁症组(P<0.05).而IL-2、sIL-6R低于抑郁症组(P均小于0.05).③精神分裂症组治疗前后血浆IL-2变化率与PANSS总分减分率正相关(r=0.64,P<0.001);抑郁症组治疗前后血浆IL-2和IL-6的变化率均与HAMD总分减分率正相关(r=0.42,P:0.02;r=0.54,P=0.002).结论 精神分裂症和抑郁症细胞因子均存在异常,提示二者可能存在共同的病理机制,但细胞因子表达的差异可能与二者存在不同的生物学基础有关.     

利培酮和氯氮平对首发精神分裂症患者血浆细胞因子的影响

目的 比较利培酮和氯氮平对首发精神分裂症患者血浆细胞因子影响的差异。方法 用酶联免疫吸附法(ELISA)测定利培酮和氯氮平两组各30例患者治疗6周前后的血浆白细胞介素-2(IL-2)、可溶性白细胞介素-2受体(sIL-2 R)、白细胞介素-6(IL-6)及可溶性白细胞介素-6受体(sIL-6R)的浓度,两组间进行比较,每组治疗前后各自进行比较。结果 两组间比较,血浆细胞因子水平无显著性差异(P>0.05);治疗前后各自进行比较,每组血浆IL-2及sIL-6R水平显著下降(P<0.05),IL-6水平显著升高(P<0.05),sIL-2R治疗前后无显著性差异(P>0.05)。结论 利培酮和氯氮平治疗均对首发精神分裂症患者的IL-2、IL-6及sIL-6R水平产生显著性影响,对sIL-2R水平影响不显著;利培酮和氯氮平对首发精神分裂症患者细胞因子水平的影响基本一致。     

急性Guillain-Barre综合征患者血清sIL-2R和sIL-6R水平的测定

目的探讨可溶性白细胞介素2受体(sIL-2R)和可溶性白细胞介素6受体(sIL-6R)在急性Guillain-Barre综合征(GBS)发病中的作用.方法采用ELISA方法测定32例GBS患者和30名正常对照者血清sIL-2R及sIL-6R 水平. 结果 GBS患者血清sIL-2R和sIL-6R水平明显高于正常对照组(P<0.01,P<0.05),重型和极重型患者明显高于轻型及中型患者(P<0.01,P<0.05),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<0.05).结论 sIL-2R和sIL-6R水平的高低可作为判断GBS病情变化的指标之一.     

阿尔茨海默病患者血清IL-10和sIL-6R水平的变化

目的 探讨阿尔茨海默病(Alzheimer disease,AD)患者血清白细胞介素-10(interleukin-10,IL-10)、可溶性白细胞介素-6受体(soluble interleukin-6 receptor．sIL-6R)水平变化及其与痴呆严重程度的关系。方法 采用双抗体夹心ELISA法检测46例AD患者(AD组)、33名年龄匹配健康者(对照组)和40例脑梗死患者(CI组)血清IL-10、sIL-6R水平。结果 AD患者血清IL-10水平较正常对照组和CI组均明显降低，但对照组与CI组间差异无显著性。AD患者血清sIL-6R水平较正常对照组明显升高并随痴呆程度加重而不断上升；CI组中血清sIL-6R水平也明显高于对照组．但AD组和CI组间差异无显著性。结论 AD患者血清IL-10和sIL-6R水平的变化提示免疫炎性机制参与了AD的发病。     

急性脑血管病患者血清NO、sIL—2R含量变化及临床意义

目的：探讨急性脑血管病（ACVD）患者血清中一氧化氮（NO）和可溶性白细胞介素2受体（sIL-2R)水平的动态变化及临床意义。方法：NO采用分光光度比色法测定；sIL-2R采用ELISA双抗体夹心法测定。结果：急性脑血管病患者急性期血清NO和sIL-2R均显著高于正常对照组（P＜0.01)，并且依神经功能缺损积分重型组明显高于轻型组（P＜0.05)；两周后复查，好转组NO较急性期显著下降，接近正常对照组（P＞0.05)，而sIL-2R较急性期下降，但仍高于正常对照组（0.05＞P＞0.01)。结论：NO参与了脑缺血再灌注的损伤过程；急性脑血管病患者存在着免疫激活，检测NO和sIL-2R对判断ACVD病情、推测预后有重要临床价值。     

格林—巴利综合征患者血清TNF和sIL—2R水平

目的:探讨肿瘤坏死因子(TNF)和可溶性白细胞介素2受体(sIL-2R)在格林-巴利综合征(GBS)发病中的作用及其临床意义。方法:采用双抗体夹心ELISA法对28例GBS患者和36例正常对照血清TNF及sIL-2R水平进行了检测。结果:GBS组血清TNF及sIL-2R水平显著高于正常对照组,血清TNF及sIL-2R水平变化与GBS病情及预后密切相关,恢复期血清TNF及sIL-2R水平显著降低。结论:TNF及sIL-2R参与了GBS的发病过程,检测血清TNF及sIL-2R水平对判定GBS病情及预后有一定的临床意义。     

精神分裂症患者可溶性白细胞介素-2受体测定及其临床意义

目的 探讨精神分裂症患者血清可溶性白细胞介素-2受体（SIL-2R）水平及其临床意义。方法 用酶联免疫试验检测42例首发精神分裂症患者治疗前后及正常人SIL-2R含量,并进行有关量表评定。结果 精神分裂症患者治疗前SIL-2R明显高于正常组（P<0.05）,男女患者间无差异;Ⅰ型精神分裂症血清SIL-2R浓度显著高于Ⅱ型和混合型（P<0.05）,后两者之间无显著性差异;治疗前,SIL-2R浓度与起病年龄呈负相关（r=-0.469,P<0.05）,与阴性和阳性症状量表（PANSS）总分呈正相关（r=0.446,P<0.05）;氯氮平和利培酮能显著升高血清SIL-2R浓度（P<0.01,P<0.05）;此外,治疗后血清SIL-2R水平升高与病程,治疗前的SIL-2R和PANSS总分显著相关。结论 血清SIL-2R升高可能与精神分裂症发病有关,亦可能成为其临床亚型分布和早期病情严重程度评价的新指标。非典型抗精神病药（尤其是氯氮平）可能通过升高SIL-2R血清浓度达到免疫抑制作用。     

Immune-inflammatory markers in schizophrenia: comparison to normal controls and effects of clozapine

The purpose of this study was to investigate immune-inflammatory markers in schizophrenia and the effects of chronic treatment with clozapine, an atypical antipsychotic agent, on these variables. Toward this end, we measured interleukin-6 (IL-6), soluble IL-6 receptor (sIL-6R) and sIL-2R in the blood of 26 normal controls and 14 schizophrenic patients before and after treatment with clozapine. The sIL-2R and IL-6 levels were significantly higher in younger (<35 years) schizophrenic subjects than in normal controls and older (≥ 35 years) schizophrenic subjects. The sIL-6R levels were significantly lower in schizophrenic subjects than in normal controls. Chronic treatment with clozapine significantly increased the blood concentration of sIL-2R; the increases in the latter were significantly related to the dose of clozapine but not to changes in severity of positive or negative symptoms. We conclude that: (a) schizophrenia in younger people is accompanied by increased IL-6 and sIL-2R secretion; and (b) subchronic treatment with clozapine increases sIL-2R levels. Increased plasma sIL-2R may be one mechanism by which neuroleptics exhibit their immunosuppressive effects.     

Correlations of Kynurenic Acid, 3-Hydroxykynurenine,sIL-2R,IFN-α, and IL-4 with Clinical Symptoms During Acute Relapse of Schizophrenia

Several lines of evidence suggest that up-regulation of immune response and alterations of kynurenine pathway function are involved in pathogenesis of schizophrenia. Correlations among clinical status (using PANNS, SANS and SAPS scales) and blood levels of kynurenic acid (KYNA), 3-hydroxykynurenine (3-HK) and levels of selected immunoactive molecules, soluble interleukin-2 receptor (sIL-2R), interferon-α (IFN-α) and IL-4 were analyzed in 51 chronic schizophrenia patients during acute relapse, after four weeks of therapy and at remission. KYNA levels were significantly lower in comparison with controls (N=45) throughout the study, whereas 3-HK did not differ from controls at admission and during therapy, but increased at remission. The KYNA/3-HK ratio and IL-4 levels, but not sIL-2R and IFN-α levels, were consistently decreased in schizophrenia patients at all analyzed time points. KYNA level and KYNA/3-HK ratio measured at admission correlated negatively with the duration of illness, whereas 3-HK level correlated negatively with the improvement of SANS score at discharge. sIL-2R level before treatment was positively linked with number of relapses. In the subgroup of patients with poor response to pharmacotherapy, treated with clozapine later on, initial KYNA level and the ratio KYNA/3-HK correlated negatively with number of relapses. Positive association of sIL-2R level with number of relapses was also evident in this subgroup. Furthermore, among these patients, starting IFN-α level was negatively linked with the improvement of total PANSS score at discharge. Presented here data support the concept of disturbed kynurenine pathway function in schizophrenia and suggest that assessment of KYNA and 3-HK levels during acute relapse might be useful in prediction of response to antipsychotic therapy. Deficit of peripheral KYNA and higher 3-HK levels could be associated with more severe symptoms of schizophrenia. Further studies with larger samples size are needed to validate our results.     

Plasma-soluble interleukin-2 and transferrin receptor in schizoprenia and major depression

This study was carried out to examine some components of in vivo immune function in major depression and schizophrenia. Toward this end, plasma concentrations of interleukin-1 (IL-1) and IL-6, soluble IL-2 receptor (sIL-2R), and transferrin receptor (TfR) were measured in 28 normal controls, 11 schizophrenics and 13 major-depressed patients. Schizophrenic and major-depressed patients showed significantly higher plasma sIL-2R and TfR than normal controls. There was a trend toward higher plasma IL-6 in the psychiatric patients, and particularly in schizophrenic patients, than in normal volunteers. In normal controls and in the total study group, there were highly significant and positive correlations between plasma TfR and sIL-2R concentrations. It is suggested that schizophrenia and major depression are characterized by immune disorders that may indicate activation of cell-mediated immunity such as T-cell activation.     

Effect of neuroleptic administration on serum levels of soluble IL-2 receptor-alpha and IL-1 receptor antagonist in schizophrenic patients

Activation of the inflammatory response system has been reported in schizophrenia. Levels of serum IL-1 receptor antagonist (IL-1ra) and soluble IL-2 receptor (sIL-2R(alpha)) were studied in 32 schizophrenic and 22 age- and sex-matched healthy subjects before and after an 8-week treatment protocol. Psychopathology was assessed with the Positive and Negative Syndrome Scale (PANSS). At weeks 0 and 8, sIL-2R(alpha) levels were significantly higher than in the schizophrenic patients, as well as in a neuroleptic-naive subgroup, than in controls. Patients' sIL-2R(alpha) levels did not vary significantly between weeks 0 and 8. IL-1ra levels in controls did not differ significantly from those in patients at week 0 but were significantly lower at week 8. The patients' serum IL-1ra levels varied significantly between weeks 0 and 8. IL-1ra levels were significantly higher in the subgroup of neuroleptic-naive patients at week 0 than in controls. Levels of sIL-2R(alpha) at week 0 were positively correlated with PANSS positive and negative symptom scores at week 8, and levels at week 8 were positively correlated with PANSS total, positive symptom, and negative symptom scores at week 8. IL-1ra levels at week 0 were positively correlated with PANSS scores at week 8. There were positive correlations between both delta (baseline values minus endline values) IL-1ra and delta sIL-2R(alpha) levels and delta PANSS negative symptoms. The results provide evidence for immune activation in some schizophrenic patients and suggest that medication differentially affects the production of sIL-2R(alpha) and IL-1ra.     

Association of plasma IL-6 and soluble IL-6 receptor levels with the Asp358Ala polymorphism of the IL-6 receptor gene in schizophrenic patients

Recent studies indicate a role of excessive interleukin-6 (IL-6) signaling in the pathogenesis of schizophrenia. A previous study reported a significant association of schizophrenia with the IL-6 receptor (IL-6R) gene Asp358Ala polymorphism, which is known to regulate circulating IL-6 and soluble IL-6R (sIL-6R) levels in healthy subjects. To further examine the influence of the polymorphism in schizophrenic patients, we compared the plasma levels of IL-6 and sIL-6R between schizophrenic patients and healthy controls for each genotype of the Asp358Ala polymorphism. Asp358Ala genotyping and plasma IL-6 level measurements were performed in 104 patients with schizophrenia and 112 healthy controls. Of these participants, 53 schizophrenic patients and 49 controls were selected for the measurement of plasma sIL-6R levels. A two-way factorial analysis of covariance was performed with the transformed plasma levels as the dependent variable, diagnosis and genotype as independent variables, and sex and age as covariates. No significant diagnosis × genotype interaction was observed for IL-6 and sIL-6R levels. The Ala allele of Asp358Ala was significantly associated with higher levels of both IL-6 and sIL-6R. IL-6 levels were significantly elevated in schizophrenic patients compared to those in controls, whereas no significant difference in sIL-6R levels was observed between schizophrenic patients and controls. Our findings suggest that the presence of schizophrenia is associated with elevated IL-6 levels, whereas sIL-6R levels are mainly predetermined by the Asp358Ala genotype and are not associated with the disease status. Increased IL-6 levels without alterations in sIL-6R levels may result in excessive IL-6 signaling in schizophrenia.     

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.     

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.     

雷公藤多甙对格林-巴利综合征患者IL-6及其可溶性受体的影响

目的　探讨白细胞介素 (IL 6 )及其可溶性受体 (sIL 6R)在格林 巴利综合征 (GBS)发病中的作用及免疫抑制性药物对其影响。方法　按Asbury标准选择GBS患者 4 3例 ,并进行病情严重程度分级 (0～Ⅴ级 )。其中Ⅱ级 13例 ,Ⅲ级 2 3例 ,Ⅳ级 7例。按分层随机原则 ,将GBS者分为 2组 ,分别用肾上腺皮质类固醇 (激素 )和雷公藤多甙治疗 ,在开始前、治疗后第 8周各按统一标准进行评估 1次 ,并取静脉血和脑脊液 (CSF)配对标本 2mL ,用ELISA法测定sIL 6R和双抗体夹心ELISA法测定IL 6。结果　 (1)病初GBS者血清IL 6、sIL 6R分别为 (6 9.73± 2 5.2 5)ng/L和 (4 6 .6 5± 11.59) μg/L ,明显高于对照组的 (17.94± 5.6 6 )ng/L和 (2 9.2 5± 11.0 4 )μg/L(t =13.16 ,7.33,P <0 .0 0 1) ,此外CSFIL 6、sIL 6R分别为 (14.33± 6 .6 9)ng/L和 (9.4 5± 0 .98) μg/L ,亦明显高于对照组的 (3.35± 2 .79)ng/L和 (1.38± 0 .50 ) μg/L(t=10 .0 2 ,4 8.4 8,P <0 .0 0 1)。(2 )病初GBS者CSFIL 6、sIL 6R与病情严重程度分级相关密切 (r=0 .6 7,0 .4 8,P <0 .0 1)。(3)雷公藤多甙与激素治疗后两组临床症状均有不同程度的改善。但雷公藤多甙组临床严重程度分级进步 1级以上者为 90 .3% ,明显高于激素组的6 1.9% (x2 =5.0 6 ,P     

脑星形胶质瘤患者血清s—IL—2R水平变化

采用双抗体夹心ELISA法对32例脑星形胶质瘤患者和45例正常对照血清可溶性白细胞介素2受体（SIL－2R）水平进行检测，其中21例患者于术后1个月进行复查。结果显示脑星形胶质瘤组血清SIL－2R水平明显高于正常对照组，血清SIL－2R水平变化与肿瘤病理级别密切相关，术后1个月血清SIL－2R水平显著降低。上述结果提示血清SIL－2R水平变化与脑星形胶质瘤消长密切相关，检测SIL－2R对判断脑星形胶质瘤病理级别及预后有一定的临床参考价值。     

精神分裂症患者治疗前血清MCP-1水平预测利培酮疗效

背景:精神分裂症是一种慢性致残性疾病,其发病及治疗可能与炎性细胞因子有关.目前细胞因子预测抗精神病药物疗效的研究尚少.目的:研究细胞因子对抗精神病药物疗效的预测作用.方法:采用横断面与自然观察随访相结合的方法,(1)对比精神分裂症患者组(n=64)基线期和正常对照组(n=53)血清IL-1β、TNF-α和MCP-1水平;(2)探索基线期细胞因子水平对奥氮平或利培酮单药治疗效果的影响.结果:(1)精神分裂症患者治疗前血清MCP-1水平明显高于健康对照组(t=2.62,p=0.010),IL-1β(t=1.43,p=0.154)、TNF-α(t=0.79,p=0.434)未见变化;(2)精神分裂症患者治疗前MCP-1水平与利培酮单药治疗4周后PANSS量表一般病理评分的减少量呈显著负相关(r=-0.658;p﹤0.001),但在奥氮平组中则未发现(r=-0.031;p=0.855);(3)纳入性别、年龄、受教育年限和BMI后等影响因素后,多元线性回归分析发现,基线血清MCP-1水平可作为利培酮单药治疗效果的独立预测因子(校正R2=0.409,β=-0.658,p﹤0.001).结论:MCP-1可能参与精神分裂症的发生,治疗前血清MCP-1水平可能是利培酮疗效预测的生物标记物.