抑郁症患者的甲状腺功能和细胞因子的研究

目的　探讨抑郁症患者甲状腺功能和细胞免疫功能异常的关系。方法　采用酶联免疫吸附法 (ELSIA)检测 5 8例抑郁症和 30名健康对照的血清游离T3、T4、TSH、IL 2、sIL 2R、IL 10、IL 12水平。结果　抑郁症患者组和对照组间血清T3、T4、TSH、IL 2、sIL 2R、IL 10、IL 12水平无明显差异 (P>0 .0 5 ) ;分型比较发现 ,双相组血清T3水平明显低于对照组 (P <0 .0 5 ) ,T3水平与疾病的严重程度呈显著负相关关系 (P <0 .0 5 ) ;单相组IL 2水平明显低于对照组 (P <0 .0 5 ) ,IL 2水平与T3呈显著负相关关系。结论　单、双相抑郁的病因和发病机制存在免疫或内分泌方面的异质性 ,双相抑郁存在甲状腺功能低下 ,单相抑郁存在由IL 2介导的免疫激活现象。     

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     

Alzheimer病患者血清和脑脊液中IL-6及sIL-6R水平的研究

目的　探讨Alzheimer病 (AD)患者血清和脑脊液 (CSF)中白细胞介素 6 (IL 6 )及白细胞介素 6受体 (sIL 6R)水平的变化。方法　采用双抗体夹心酶联免疫吸附试验 (ELISA)分别对 11例AD患者、13例血管性痴呆 (VD)患者及 13例正常对照者 (NC)血清和CSF中IL 6及sIL 6R水平进行了检测。结果　 (1)CSF中IL 6和sIL 6R水平各组检测的阳性率均较高 ,依次为AD >VD >NC ,痴呆两组与对照组比较均有显著性差异 (均P <0 .0 1)。 (2 )痴呆两组患者血清sIL 6R的阳性率明显高于对照组 (均P <0 .0 1)。 (3)CSF中IL 6和sIL 6R水平存在显著正相关 (r=0 .75 ,P <0 .0 5 ) ,与MMSE量表得分呈负相关 (r =- 0 .6 9,P <0 .0 5 )。结论　CSF中IL 6水平与痴呆严重程度有关 ,检测CSF中IL 6更能反映痴呆患者的免疫炎性改变 ,不仅为AD的慢性免疫炎症机制提供了理论依据 ,也将为AD的诊断和治疗提供新的途径     

血浆IL-6、sIL-6R及IL-13与首发精神分裂症临床特征的关系

目的　探讨首发精神分裂症患者血浆IL 6、sIL 6R、IL 13水平及其与精神分裂症临床特征之间的相关关系。方法　采用酶联免疫吸附法 (ELISA)测定 3 0例首发精神分裂症患者血浆IL 6、sIL 6R及IL 13水平 ,并用阳性和阴性症状评定量表 (PANSS)评定精神症状严重程度。结果　精神分裂症患者血浆IL 6及sIL 6R水平显著高于正常对照组 (P <0 0 5 ) ;而血浆IL 13水平显著低于正常对照组 (P <0 0 5 )。患者血浆sIL 6R水平与阳性症状分 (P分 )呈正相关 (r=0 3 79,P =0 0 2 0 ) ;血浆IL 13水平与阴性症状分 (N分 )呈负相关 (r=-0 60 2 ,P =0 0 0 0 ) ,IL 13与PANSS总分呈负相关 (r=-0 3 3 4,P =0 0 3 5 )。结论　精神分裂症患者可能存在免疫功能异常 ,sIL 6R可能作为反映精神分裂症阳性症状严重程度的免疫指标之一 ,IL 13可能作为反映精神分裂症阴性症状严重程度的免疫指标之一。     

利培酮对精神分裂症认知功能和血清细胞因子水平的影响

目的探讨利培酮对精神分裂症认知障碍的影响及其与血清白介素-2(IL2)、可溶性白介素-2受体(sIL2R)水平变化的关系。方法对符合中国精神障碍分类与诊断标准第3版(CCMD-3)精神分裂症诊断的60例患者予利培酮治疗6周;治疗前后分别采用数字划销测验(CT)、修订韦氏成人记忆量表(WMS-RC)、威斯康星卡片分类测验(WCST)评估注意功能、记忆功能和执行功能,同时采用酶联免疫吸附法(ELISA)检测血清IL2、sIL2R水平。对60名健康人(对照组)进行相同的认知功能和血清细胞因子检测。结果治疗前精神分裂症患者组认知功能测验成绩显著差于对照组(P<0.01),血清IL2水平显著高于对照组(P<0.05)。通过6周的利培酮治疗,CT的净分及WMS-RC的记忆商数均有显著提高,CT的失误率及WCST的总测验次数、持续错误数、随机错误数均显著下降,同时血清IL2水平显著降低,而sIL2R水平变化不明显;治疗前患者的失误率与血清IL2水平呈显著正相关(P<0.05),记忆商数与血清IL2水平呈显著负相关(P<0.05),治疗6周末失误率下降值和记忆商增加值均与血清IL2水平下降值呈显著正相关(P<0.05)。结论利培酮对精神分裂症注意、记忆功能的改善与降低的血清IL2水平相联系;精神分裂症认知功能障碍的部分特质可能与其紊乱的免疫功能(特别是细胞因子)有关。     

阿尔茨海默病患者血清和脑脊液中白细胞介素-6及白细胞介素-6受体水平的研究

目的 :探讨阿尔茨海默病 (AD)病因及发病机制。方法 :采用双抗体夹心酶联免疫吸附试验分别对AD患者血清和脑脊液(CSF)中白细胞介素 6(IL 6)及白细胞介素 6受体 (sIL 6R)水平进行检测。结果 :①AD组和血管性痴呆 (VD)组CSF中IL 6含量和阳性率明显高于对照组 (P <0 0 5和P <0 0 1) ;血清和CSF中sIL 6R含量和阳性率明显高于对照组 (P <0 0 1和P <0 0 5 )。②AD患者CSF中IL 6和sIL 6R水平存在显著正相关 (r =0 75 ,P <0 0 5 ) ,与MMSE量表得分呈负相关 (r =-0 69,P <0 0 5 )。结论 :CSF中IL 6可能主要来源中枢神经系统的自身合成 ,并与痴呆的严重程度有关。检测CSF中IL 6与sIL 6R可为痴呆诊断提供依据。     

重症肌无力患者血清sIL—2R水平检测

对100例临床确诊为重症肌无力（MG）、血清乙酰胆碱受体抗体阳性的患者进行血清可溶性白细胞介素-2受体（sIL－2R）检测。结果表明：（1）MG患者治疗前血清中sIL-2R水平与正常对照组无显著性差异。其中全身型MG组较正常对照组sIL－2R水平明显增高，但眼肌型MG组与正常对照组间无显著差异；（2）全身型MG组经强的松治疗4周后sIL－2R水平明显下降；（3）胸腺瘤切除术后1年后sIL－2R水平较术前显著降低。上述结果提示sIL－2R水平可能与MG疾病状态有密切关系。     

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     

脑肿瘤患者可溶性白介素2受体及肿瘤坏死因子α的测定

目的　研究脑肿瘤患者术前及术后血清中可溶性白介素 2受体及肿瘤坏死因子α的水平及其表达意义。方法　在术前、术后 2周、术后 3个月分别测定了 4 7例星形细胞瘤、2 2例脑膜瘤、2 5例脑转移瘤血清中可溶性白介素 2受体及肿瘤坏死因子α的水平。结果　术前脑肿瘤患者的白介素 2受体、TNF -α较正常均明显升高。术后 2周及 3个月 ,脑膜瘤患者的sIL - 2R、TNF -α较术前均明显下降。星形细胞 3— 4级、转移瘤患者的白介素 - 2R、TNF -α的测定较术前改变不明显。将死亡与未死亡患者术前的sIL - 2R进行比较 ,我们发现死亡组的sIL - 2R的测定明显高于未死亡组。结论　sIL - 2R及TNF -α的表达与肿瘤类型有关。sIL - 2R及TNF -α可作为估计脑肿瘤预后的指标     

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。     

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。     

Serum and CSF levels of IL-2, sIL-2R, TNF-alpha, and IL-1 beta in chronic progressive multiple sclerosis: expected lack of clinical utility

We measured interleukin-2 (IL-2), soluble IL-2 receptor (sIL-2R), tumor necrosis factor-alpha (TNF-alpha), and interleukin-1 beta (IL-1 beta) by ELISA in paired sera and CSF from 50 chronic progressive multiple sclerosis (CPMS) patients during worsening disability, 19 patients with other neurologic diseases (OND), and in sera from 40 healthy volunteers. In the CPMS patients, 28% (14/50), 10% (5/50), 16% (8/50), and 6% (3/50) had elevated serum levels of IL-2, sIL-2R, TNF-alpha and IL-1 beta, respectively, compared with healthy controls. The only analyte we detected in the CSF was IL-2 in 1 CPMS patient (1/50, 2%). We also saw elevated serum sIL-2R in 16% (3/19) of OND patients. We found no significant difference in mean levels of serum sIL-2R between the 3 groups. Our study, the largest to date of CPMS patients, shows that serum and CSF levels of IL-2, sIL-2R, TNF-alpha, or IL-1 beta are not sensitive for, and the serum sIL-2R level is not specific for, CPMS. Therefore, measurement of these analytes will not be clinically useful for therapeutic or prognostic purposes in the majority of CPMS patients.     

Lipid Peroxidation and Immune Biomarkers Are Associated with Major Depression and Its Phenotypes,Including Treatment-Resistant Depression and Melancholia

To examine immune-inflammatory and oxidative (I&O) biomarkers in major depression (MDD) and its related phenotypes, we recruited 114 well-phenotyped depressed patients and 50 healthy controls and measured serum levels of interleukin (IL)-1α, soluble IL-1 receptor antagonist (sIL-1RA), soluble IL-2 receptor (sIL-2R), soluble IL-6 receptor (sIL-6R), soluble tumor necrosis factor receptor 60 and 80 kDa (sTNF-R1/R2), and thiobarbituric acid reactive substances (TBARS). Obtained results indicate that MDD is characterized by increased sIL-1RA, sTNF-R1, and TBARS concentrations. Melancholic depression is associated with increased sIL-6R but lowered IL-1α levels. A current episode of depression is accompanied by significantly increased sIL-6R compared to the remitted state. Treatment-resistant depression (TRD) is accompanied by increased sIL-6R and TBARS but lowered sTNF-R2 levels compared to non-TRD patients. These immune markers are not significantly correlated with Hamilton Depression Rating Scale (HDRS), Montgomery-Asberg Depression Scale (MADRS), number episodes, or age at onset. Our findings show that increased sIL-1RA, sTNF-R1, and TBARS levels may be trait markers of depression, while increased sIL-6R levels may be a state marker of melancholia and an acute phase of depression. MDD is accompanied by increased lipid peroxidation and simultaneous activation of immune pathways, and the compensatory anti-inflammatory reflex system (CIRS). TRD is characterized by highly increased oxidative stress and probably increased TNFα and IL-6 trans-signalling. Novel treatments for major depression should target oxidative stress pathways, while new treatments for TRD should primary target lipid peroxidation and also activated immune-inflammatory pathways.     

Elevated serum interleukin-6 (IL-6) and IL-6 receptor concentrations in posttraumatic stress disorder following accidental man-made traumatic events.

BACKGROUND: Recently, it has been reported that serum interleukin-1 beta (IL-1 beta), but not soluble IL-2 receptor (sIL-2R), concentrations were significantly higher in patients with posttraumatic stress disorder (PTSD) than in normal volunteers, and that psychological stress in humans is associated with increased secretion of proinflammatory cytokines, such as IL-6. METHODS: The aim of the present study was to examine the inflammatory response system in patients with PTSD through measurements of serum IL-6, sIL-6R, sgp130 (the IL-6 signal transducing protein), sIL-1R antagonist (sIL-1RA; an endogenous IL-1 receptor antagonist), CC16 (an endogenous anticytokine), and sCD8 (the T suppressor-cytotoxic antigen). RESULTS: Serum IL-6 and sIL-6R, but not sgp130, sIL-RA, CC16, or sCD8, concentrations were significantly higher in PTSD patients than in normal volunteers. Serum sIL-6R concentrations were significantly higher in PTSD patients with concurrent major depression than in PTSD patients without major depression and normal volunteers. There were no significant relationships between serum IL-6 or sIL-6R and severity measures of PTSD. CONCLUSIONS: The results suggest that PTSD is associated with increased IL-6 signaling. It is hypothesized that stress-induced secretion of proinflammatory cytokines is involved in the catecholaminergic modulation of anxiety reactions.     

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.     

Immune activation in multiple sclerosis: study of IL-2, sIL-2R, and gamma-IFN levels in serum and cerebrospinal fluid

Serum and cerebrospinal fluid (CSF) levels of interleukin-2 (IL-2), soluble IL-2 receptor (sIL-2R), and gamma-interferon (gamma-IFN) were measured in multiple sclerosis (MS) patients, human immunodeficiency virus type 1 (HIV-1)-infected patients and normal controls (NC). Increased levels of both IL-2 and sIL-2R were found in MS serum. Moreover, 11 of 50 MS patients showed detectable levels of IL-2 in the CSF. HIV-1-infected patients had increased levels of sIL-2R in serum and, less frequently, in the CSF. gamma-IFN was never detected in serum and CSF of all the patients studied. These findings confirm preliminary reports, further stress a systemic T-cell activation in MS, and support the hypothesis that an immunologic disorder exists in such patients.     

In-vitro immunomodulatory effects of haloperidol and perazine in schizophrenia.

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.     

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.     

Immunoendocrine aspects of major depression

Recently, a complete bidirectional circuit between the immune and neuroendocrine systems has been documented. Previous reports from this laboratory have shown that there are complex reciprocal relationships between immune and hypothalamic-pituitary-adrenal (HPA)-axis function in major depression. To further examine the immune-endocrine relationships, this study investigates plasma baseline cortisol and prolactin secretion in relation to plasma interleukin-6 (IL-6) and soluble IL-2 receptor (sIL-2R) levels in 34 healthy controls and 56 major depressed patients. There were significant positive correlations between IL-6 or sIL-2R and plasma cortisol in major depressed subjects and in the combined group of major depressed and healthy subjects. There were also significant positive correlations between plasma prolactin and sIL-2R concentrations in major depressed subjects and in the combined groups of normal and major depressed subjects.