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.     

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。     

难治性颞叶癫痫脑组织IL-6、IL-6受体及sIL-6R、 sgp130的表达及意义

目的 探讨IL-6、IL-6膜受体(IL-6R)及其下游信号转导相关分子在颞叶癫痫(TLE)发生中的作用. 方法 选择自2010年1月至2010年12月在第三军医大学新桥医院神经外科行手术治疗的TLE患者40例(TLE组),同期行手术治疗的外伤、高血压脑出血等患者40例(对照组);收集其手术过程中切除的颞叶组织.利用RT-PCR、ELISA等方法分析IL-6、IL-6R、sIL-6R以及sgp130的mRNA或蛋白水平的表达变化情况. 结果 TLE组和对照组中均可检测到IL-6和IL-6R mRNA的表达,但TLE组致病灶中IL-6和IL-6R mRNA水平均显著高于对照组,差异有统计学意义(P＜0.05).ELISA结果提示,sIL-6R在TLE组致痫灶中的表达量与对照组比较明显增高,差异有统计学意义(P＜0.05);sgpl30的含量略高于对照组,差异没有统计学意义(P＞0.05). 结论 局部高浓度的IL-6通过经典信号转导或者跨信号转导机制作用于TLE病灶细胞,影响这些细胞的生物学功能,参与癫痫发生过程.     

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。     

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.     

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。     

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。     

脑外伤患者一氧化氮与白介素-2受体变化的研究

目的探讨颅脑外伤后血浆一氧化氮(NO)含量水平与可溶性白细胞介素-2受体(sIL-2R)的关系.方法应用荧光法、双抗体夹心间接ELISA法分别检测53例颅脑损伤患者血浆中NO、sIL-2R的含量变化.结果重型、中型脑外伤后血浆NO、sIL-2R均与对照组差异非常显著(P<0.001),轻型组NO差异显著(P<0.05);sIL-2R升高非常显著(P<0.01).NO和sIL-2R相关性与颅脑损伤的程度分析,呈显著正相关(r＝0.475P<0.01).结论血浆中NO与sIL-2R的检测有助于评价颅脑外伤患者病情的严重程度和预后.     

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=0446,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.     

Soluble interleukin-2 receptor levels correlated with positive symptoms during quetiapine treatment in schizophrenia-spectrum disorders

Background

Some but not all antipsychotics have been shown to modulate plasma cytokine levels in schizophrenia patients. Thus far, the most consistent finding has been the increase in plasma levels of soluble interleukin (IL)-2 receptor (sIL-2R) associated with clozapine treatment. Quetiapine is a second-generation antipsychotic with a pharmacological profile similar to that of clozapine, but its immunomodulatory effects have not been investigated in schizophrenia yet. The purpose of this exploratory study was to examine the changes in plasma levels of sIL-2R in schizophrenia during quetiapine treatment and association with psychopathology.

Methods

Participants were 29 schizophrenia-spectrum disorder patients (DSM-IV criteria), and 28 healthy controls. Patients had a comorbid substance use disorder (cannabis > alcohol > cocaine), since quetiapine is increasingly used in this population of dual diagnosis. No participant suffered from infection or overt inflammatory diseases. On baseline, patients taking mostly second-generation antipsychotics were switched to quetiapine for a 12-week open-label trial. Five patients were drop-outs. Mean dose of quetiapine for trial completers (n = 24) was 466.6 mg ± 227.3. Psychiatric variables were evaluated with the Positive and Negative Syndrome Scale and the Calgary Depression Scale for Schizophrenia. Plasma sIL-2R levels were assessed at baseline, weeks 6 and 12 in patients, and in healthy controls, using sandwich immunoassay. Plasma IL-6 and IL-1 receptor antagonist (IL-1RA) were measured for comparison purposes.

Results

On baseline, plasma sIL-2R, IL-6 and IL-1RA levels were higher in dual-diagnosis patients, compared to controls. Plasma sIL-2R further increased after quetiapine treatment (p = 0.037), while plasma IL-6 and IL-1RA did not change. Clinical improvements were observed in positive, negative and depressive symptoms, and substance abuse severity (all p < 0.01). Interestingly, changes in sIL-2R levels during treatment were inversely correlated with changes in positive symptoms (r = − 0.524; p = 0.009). That is, increases in sIL-2R levels were associated with reductions in positive symptoms.

Conclusion

These data show that quetiapine elevates, like clozapine, sIL-2R levels in schizophrenia. Furthermore, the results suggest that sIL-2R alterations in schizophrenia rely on complex interplays between antipsychotics and the positive symptoms of the disorder. Future randomized controlled trials involving larger samples of schizophrenia patients are warranted to determine whether changes in plasma sIL-2R are quetiapine-related.     

In vivo relationship of interleukin-2 and soluble IL-2 receptor to blood-brain barrier impairment in patients with active multiple sclerosis

Interleukin (IL)-2 has well-recognized effects on cerebral endothelial cells and, therefore, may mediate disruption of the blood-brain barrier in patients with multiple sclerosis (MS). To evaluate the in vivo relationship of the IL-2 system to blood-brain barrier impairment in MS, levels of IL-2 and soluble IL-2 receptors (sIL-2R) in cerebrospinal fluid (CSF) and serum samples from 50 patients with active MS and 49 controls were correlated with values of the CSF to serum albumin ratio. Intrathecal levels of IL-2 and sIL-2R were significantly higher in MS compared with the control groups and correlated with albumin ratios in MS patients. Intrathecal levels of IL-2 and sIL-2R also correlated with the degree of barrier damage in these patients. It is suggested that intrathecal levels of IL-2 and sIL-2R are related to barrier impairment in MS and may be important in understanding some of the pathological changes of this condition.     

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.     

Plasma soluble interleukin-2-receptor in depression: relationships to plasma neopterin and serum IL-2 concentrations and HPA-axis activity

The present study examined the plasma concentration of the soluble interleukin-2-receptor (sIL-2R) in depressed subjects in relation to hypothalamic pituitary adrenal (HPA) axis function and plasma neopterin and serum IL-2 concentrations. Plasma sIL-2R concentration was significantly higher in depressed patients (n = 47) than in controls (n = 19). There were no significant correlations between plasma sIL-2R and severity of illness. In the depressed subjects, there was a highly significant relationship between plasma sIL-2R and neopterin concentrations. Depressed patients with pathologically increased plasma neopterin levels had significantly higher plasma sIL-2R values than those with normal serum neopterin. There were no significant relationships between plasma sIL-2R and indices of HPA-axis function in depression. There was no significant effect of dexamethasone administration on sIL-2R levels. Significantly more depressed subjects had measurable serum IL-2 levels than normal controls. Our data support the notion that a moderate activation of cell-mediated immunity may play a role in the pathophysiology of depression.     

以阳性、阴性症状为主的首发精神分裂症患者血清蛋白因子水平与PANSS评分的相关性

目的探讨以阳性、阴性症状为主的首发精神分裂症患者血清白细胞介素-6(IL-6)、钙结合蛋白S100β(S100β)、神经营养因子-3(NT-3)三种蛋白因子的浓度水平差异以及与其阳性与阴性症状量表(PANSS)评分中阳性症状、阴性症状、认知、兴奋及抑郁情绪评分之间的相关性。方法以2014年1月-2015年11月于昆明医科大学第一附属医院精神科门诊及住院的首发精神分裂症患者为患者组,选取同期来自本院体检中心的健康体检者为对照组。采用酶联免疫吸附技术(ELISA)测定44例以阳性症状为主的首发精神分裂症患者(阳性组)、38例以阴性症状为主的首发精神分裂患者(阴性组)和78名健康对照者(对照组)血清中蛋白因子IL-6、S100β、NT-3的浓度,通过PANSS对患者组和对照组的阳性症状、阴性症状、认知功能、兴奋症状及抑郁情绪进行定量评估。结果 1三组血清IL-6浓度比较,差异有统计学意义(F=31.34,P0.01),两两比较,对照组IL-6浓度低于阳性组和阴性组,阳性组低于阴性组,差异均有统计学意义(P均0.05);2三组S100β浓度比较,差异有统计学意义(F=9.19,P0.05),两两比较,阳性组、阴性组的S100β浓度均高于对照组(P均0.05),两患者组间比较差异无统计学意义(P0.05);3三组NT-3浓度比较,差异有统计学意义(F=10.45,P0.05),两两比较,阳性组、阴性组NT-3浓度均低于对照组(P均0.05),两患者组间比较差异无统计学意义(P0.05)。阳性组血清NT-3浓度与兴奋评分呈正相关(r=0.38,P0.05)。结论以阴性症状为主的首发精神分裂症患者的神经炎症反应较以阳性症状为主的患者更强烈,以阳性症状为主的首发精神分裂症患者的异常兴奋可能与其细胞营养不足有关,以阳性症状为主的首发精神分裂症的病理机制可能与以阴性症状为主的首发精神分裂症不尽相同。     

脑卒中后抑郁患者血清白细胞介素-2水平变化的研究

目的研究脑卒中后抑郁（poststroke depression，PSD）患者血清白细胞介素-2（interleutin-2，IL-2）水平变化，并探讨PSD患者的免疫功能变化。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LI-2水平；观察29例PSD患者抗抑郁治疗后血清IL-2水平变化。结果治疗前，PSD治疗组血清IL-2水平显著低于非PSD组（P〈0．01）和正常对照组（P〈0．01）；治疗后，PSD治疗组与PSD非治疗组相比，IL-2水平显著升高（P〈0．01），HAMD评分显著降低（P〈0．01）。PSD组治疗前、PSD治疗组治疗后和PSD非治疗组中，HAMD评分与血清IL-2水平呈显著性负相关。结论PSD患者血清IL-2水平明显降低，且与抑郁程度相关，提示PSD可能影响患者免疫功能的变化。     

单、双相抑郁障碍血清细胞因子水平的比较研究

目的　探讨细胞因子在单、双相抑郁障碍发病中的作用。方法　采用酶联免疫吸附法(ELSIA)检测 35例单相抑郁、2 3例双相抑郁和 30名健康对照的血清IL 2、sIL 2R、IL 10、IL 12水平。结果　单相组血清IL 2明显低于对照组和双相组 (P <0 0 5 ) ;血清IL 2水平降低与抑郁症的病程和严重程度无相关性 (P >0 0 5 )。结论　单相抑郁和双相抑郁间可能存在着不同的免疫学机制 ,在单相抑郁中存在免疫激活现象 ,IL 2可能起一定的作用     

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.