多发性硬化患者趋化因子MCP—1的表达及意义

目的 测定急性期多发性硬化(MS)患者血清及脑脊液中的趋化因子MCP—1的浓度变化，并对其结果作初步探讨。方法 用ELISA法检测20例急性期MS患者，20例其他神经系统疾患的血清/脑脊液中的趋化因子MCP—1的浓度。结果 急性期MS患者血清及脑脊液中的趋化因子MCP—1的浓度与对照组相比均下降。结论 急性期MS患者血清及脑脊液中的趋化因子MCP—1的浓度下降可能与T细胞的不同反应性有关，趋化因子可能参与MS的发病过程。     

多发性硬化患者血清单核细胞趋化蛋白-1水平动态检测

目的探讨单核细胞趋化蛋白-1与多发性硬化的关系。方法采用酶联免疫吸附试验(ELISA)动态检测44例不同分型的多发性硬化患者(MS组)和42例健康对照组(NC组)血清中单核细胞趋化蛋白-1(MCP-1)水平。结果 MS组急性期患者血清MCP-1含量明显低于稳定期和健康对照组(P<0.05);重型患者血清MCP-1含量明显低于轻型(P<0.05);MS组稳定期患者血清MCP-1含量与对照组比较差异无统计学意义(P>0.05);经甲基强的松龙冲击治疗后MS患者血清MCP-1含量明显升高(P<0.05)。结论 MCP-1可能参与了MS的免疫过程,血清MCP-1浓度可作为观察MS患者病情及判断治疗效果的可靠指标;甲基强的松龙冲击治疗的部分机制可能和调节免疫功能以及MCP-1等细胞因子平衡有关。     

难治性癫痫患者血清和脑脊液中MCP-1表达的研究

目的研究单核细胞趋化蛋白-1(monocyte chemottractant protein-1 MCP-1)在难治性癫痫患者血清和脑脊液中的表达。方法采用RT-PCR和ELISA技术测定难治性癫痫患者、非难治性癫痫患者、正常对照组血清及/或脑脊液中MCP-1 mRNA及蛋白的含量。结果难治性癫痫患者血清及脑脊液中的MCP-1 mRNA及蛋白的含量较非难治性癫痫明显升高(P<0.01),血清中含量较正常对照组明显增高(P<0.01);非难治性癫痫患者血清中MCP-1 mRNA及蛋白的含量与正常对照组比较差别无统计学意义(P>0.05)。结论MCP-1在难治性癫痫患者血清及脑脊液中均升高,MCP-1可能参与了难治性癫痫的发病过程。     

趋化因子MIP-1α和MCP-1在吉兰-巴雷综合征患者脑脊液中的表达

目的通过研究MIP-1α和MCP-1在吉兰-巴雷综合征(GBS)患者脑脊液中的表达水平,探讨种其与GBS发病的关系.方法利用双抗体夹心ELISA法测定18例GBS患者和18例非炎症性神经系统疾病患者脑脊液中MIP-1α和MCP-1的浓度.结果GBS患者脑脊液中MIP-1α浓度明显高于对照组(P＜0.01),而MCP-1浓度稍低于对照组(P＜0.05),且MIP-的α水平与脑脊液蛋白含量呈正相关(r=0.84,P＜0.01).结论MIP-1α和MCP-1可能参与GBS的发病,并发挥着不同的免疫调节作用.     

多发性硬化患者血清及脑脊液中干扰素-γ水平的研究

目的研究多发性硬化患者血清及CSF中干扰素-γ水平的变化,探讨干扰素-γ在MS发病中的作用。方法选择58例河北医科大学第二医院住院MS患者,临床表现符合Poser等制定标准的确诊(definite)或很可能(probable)MS诊断。选择40例无血缘关系的健康人,年龄、性别均与病例组匹配,近期无感染、未应用免疫抑制剂。血液及CSF标本应用双抗体夹心酶联免疫(ELISA)方法测定干扰素-γ含量。结果急性期MS组血清及脑脊液IFN-γ水平较正常对照组及缓解期MS组明显升高,且脑脊液INF-γ增高程度明显。结论 INF-γ水平在MS急性期增高,并随病情的缓解而逐渐恢复正常,说明INF-γ在MS发病过程中起促进作用。     

肺炎衣原体抗体效价与多发性硬化的相关性探讨

目的 探讨肺炎衣原体（Chlamydia pneumoniae）感染在多发性硬化（MS）发病和进展中的作用和致病机制。方法 选取急性期MS患者31例，缓解期MS患者28例及其他神经系统疾病患者30例，健康对照者30名，应用酶联免疫吸附试验测定患者和对照者血清及脑脊液中肺炎衣原体IgG和IgM抗体水平。结果 急性期MS组、缓解期MS组、其他神经系统疾病组和健康对照组的肺炎衣原体血清IgG分别为48．4％、35．7％、30．0％、23．3％；4组IgM抗体效价分别为12．9％、14．3％、20．0％、10．0％，总体比较差异无统计学意义（P〉0．05）；急性期MS组与其他神经系统疾病组的脑脊液IgG和IgM抗体效价分别为0、6．7％和0、0，差异无统计学意义（P〉0．05）。结论 肺炎衣原体的感染或重复感染与MS发病相关不紧密，可能仅为MS的伴随感染。     

急性脑血管病患者血清和脑脊液中胰岛素样生长因子-1的测定及其临床意义

目的　探讨急性脑血管病患者血清及脑脊液中胰岛素样生长因子 - 1(IGF - 1)浓度的变化及其临床意义。方法　观察 40例脑血管病患者和 2 0例正常人血清及脑脊液IGF - 1浓度。病例组 :脑梗死组2 0例 ,脑出血组 2 0例 ,所有患者均在发病后第 3天抽取静脉血 2ml,其中脑梗死组在抽血当天作腰穿抽取脑脊液 2ml。IGF - 1采用酶联免疫分析方法测定。应用SPSS统计软件包进行统计分析 ,组间比较采用t检验。结果　病例组与对照组血清中IGF - 1浓度有明显统计学差异 (P <0 .0 1) ,脑梗死组与脑出血组血清中IGF - 1浓度无统计学差异 (P >0 .0 5 )。脑梗死组与对照组脑脊液中IGF - 1浓度有明显统计学差异 (P <0 .0 1)。结论　脑梗死和脑出血患者急性期血清IGF - 1浓度明显降低 ,脑梗死组患者急性期脑脊液IGF - 1浓度明显增高。     

多发性硬化、视神经脊髓炎患者血清及脑脊液中脑源性神经营养因子与胶质细胞源性神经营养因子水平

目的 探讨多发性硬化(MS)、视神经脊髓炎(NMO)患者血清及脑脊液中脑源性神经营养因子(BDNF)、胶质细胞源性神经营养因子(GDNF)水平及其神经保护作用.方法 对62例MS、NMO患者及21例对照者进行研究,患者组复发期进行扩展残疾状态量表(EDSS)评分、MRI检查及寡克隆带测定,液相芯片分析技术检测血清及脑脊液BDNF、GDNF浓度.结果 MS、NMO患者复发期血清及脑脊液BDNF(μg/L,MS患者:5.616±0.650、0.186±0.012;NMO患者6.584±0.929、0.176±0.006)、GDNF浓度(μg/L,MS患者:0.039、0.080;NMO患者0.029、0.050)与对照组(μg/L,血清:4.374±0.501、0.040;脑脊液:0.152±0.011、0.065)比较差异无统计学意义;脑脊液BDNF与GDNF浓度水平呈正相关(r=0.756,P=0.000),血清BDNF与GDNF浓度水平呈负相关(r=-0.329,P=0.018).血清及脑脊液BDNF、GDNF浓度与EDSS评分、血脑屏障指数、Delpech指数及Tourtellotte合成率无明显相关性.有或无脑萎缩的MS、NMO患者血清及腩脊液BDNF、GDNF浓度差异无统计学意义.结论 MS、NMO患者体内BDNF与GDNF水平相关,二者可能具有协同的神经保护作用.BDNF及GDNF与NMO、MS患者血脑屏障破坏及中枢神经系统内IgG合成无关,与神经功能残疾及脑萎缩的关系仍需研究.     

多发性硬化患者病情演变与血浆和脑脊液基质金属蛋白酶-9水平的相关性

目的观察急性期多发性硬化(MS)患者血浆和脑脊液基质金属蛋白酶-9(MMP-9)水平的动态变化规律及其与临床神经功能障碍的相关性,探讨其对疾病活动性的判定价值。方法收集急性期MS患者、缓解期MS患者、健康对照各30例,神经系统非炎性疾病(NIND)17例,采用酶联免疫吸附试验法(ELISA)检测血浆和脑脊液MMP-9水平,并进行EDSS评分。结果 (1)与急性发作期初期相比,急性期MS患者第1、2周血浆MMP-9水平明显升高(P=0.019;P=0.014),第4周其脑脊液水平明显降低(P=0.014)。(2)急性期MS组血浆MMP-9水平明显高于缓解期组和健康对照组(P0.01)。(3)与NIND组比较,急性期MS组脑脊液MMP-9水平明显升高(P0.01)。(4)在MS急性期血浆与脑脊液MMP-9水平呈正相关(r=0.571,P=0.016),两者与患者同期EDSS评分之间无相关性(P0.05)。结论 (1)MS患者血浆MMP-9水平可成为监测疾病活动的指标。(2)脑脊液MMP-9水平对鉴别MS患者与NIND有一定帮助。(3)在一定程度上急性期MS组血浆MMP-9水平可以代表脑脊液中的水平。     

多发性硬化患者血清和脑脊液中白细胞介素-6的变化及其意义

本研究应用生物学方法检测27例多发性硬化（MS）患者血清和脑脊液（CSF）白细胞介素-6（IL－6）水平，以探讨IL－6在MS发病中的作用。结果显示MS患者血清IL-6水平显著高于其他非炎症性神经病（NIND）组及正常对照（NC）组，其CSFIL－6水平亦显著高于NIND组；但MS患者血清与CSFIL-6水平不呈线性相关，血清IL-6水平随病情稳定而下降。本研究结果提示IL－6可能参与MS的免疫病理过程。     

Serum and CSF levels of MCP-1 and IP-10 in multiple sclerosis patients with acute and stable disease and undergoing immunomodulatory therapies

The two chemokines, monocyte chemoattractant protein (MCP)-1 and gamma-interferon inducible protein (IP)-10, are thought to be involved in the pathogenesis of multiple sclerosis (MS). We measured MCP-1 and IP-10 levels in serum and CSF samples from 38 acute and 25 stable MS patients and from 40 controls. The latter consisted in patients with other inflammatory neurological diseases (OIND) or with non-inflammatory neurological diseases, and healthy controls. CSF MCP-1 levels exceeded those found in serum in all the patients studied as well as in healthy controls. CSF MCP-1 levels were significantly lower in acute MS [468+/-(S.E.M.) 18 pg/ml] than in stable MS (857+/-104 pg/ml). When detectable, serum and CSF IP-10 levels were significantly higher in acute MS (serum 331+/-66 pg/ml; CSF 118+/-16 pg/ml) than in stable MS (serum 69+/-7 pg/ml; CSF 25+/-2 pg/ml). Among OIND patients, those with HIV-1-associated dementia showed high serum and CSF levels of both MCP-1 and IP-10. Those with encephalitis showed high serum and CSF levels of IP-10 and CSF mononuclear pleiocytosis. We also evaluated the effects of 6-methylprednisolone or IFN-beta1a therapy on circulating MCP-1 and IP-10 levels. Neither MCP-1 nor IP-10 post-therapy levels varied significantly from baseline values. Our findings suggest that (a) MCP-1 could be constitutively produced within the brain; (b) MCP-1 and IP-10 CSF levels in acute MS vary significantly from those in stable MS, and these variations are inverse; and (c) current MS therapies do not modify circulating levels of MCP-1 and IP-10.     

IP-10 and MCP-1 levels in CSF and serum from multiple sclerosis patients with different clinical subtypes of the disease

Interferon-gamma-inducible Protein-10 (IP-10) and Monocyte Chemotactic Protein-1 (MCP-1) levels were measured by enzyme-linked immunosorbent assay (ELISA) in the CSF and in the serum from 74 patients affected by different clinical forms of Multiple Sclerosis (MS), including 39 patients with Relapsing Remitting (RR) MS in an active phase, 14 patients in a stable phase of the disease, 12 patients with Secondary Progressive (SP) MS and 9 patients with Primary Progressive (PP) MS. IP-10 and MCP-1 levels were also determined in 19 subjects with no neurological diseases or major systemic disorders, 18 patients with non-inflammatory neurological diseases, as well as in 15 patients with other inflammatory neurological diseases.IP-10 levels were significantly elevated in CSF and serum from RR and SP, but not PP-MS patients. On the contrary, MCP-1 levels were decreased in CSF and serum of all MS patients. CSF concentrations of IP-10 and MCP-1 did not significantly correlate neither with each other, nor with CSF mononuclear cell count, albumin quotient or CSF IgG index. No correlation between disease duration, clinical course or EDSS score and chemokine levels was found.IP-10 and MCP-1 undergo modifications in different subtypes of the disease: IP-10 levels in CSF and serum samples are markedly increased when inflammation is prominent, and not in PP--MS patients, where inflammation is less evident. MCP-1 decrease in CSF and serum from MS patients could be related to the regulation of T-cell polarization.     

Differential release of beta-chemokines in serum and CSF of patients with relapsing-remitting multiple sclerosis

OBJECTIVE: beta-chemokines were recently demonstrated in active MS-lesions. We tested whether MCP-1 and RANTES can also be detected in CSF and serum of patients with MS and whether release is associated with inflammatory disease activity. MATERIALS AND METHODS: CSF and serum from 34 patients with newly diagnosed relapsing-remitting MS (RR-MS), 17 patients with viral meningitis (VM) and 19 patients with non-inflammatory neurological diseases (NIND) were investigated by ELISA. RR-MS patients underwent lumbar puncture and Gd-enhanced MRI examinations within 2 days. RESULTS: MCP-1 was strong intrathecally released in all patients. Compared to NIND CSF-levels were increased in VM (P<0.001) and were decreased in RR-MS (P<0.05). RANTES was only detected in serum in all patients. Levels were higher in VM and RR-MS compared to NIND (P<0.05). A total of 14/34 RR-MS patients exhibited active Gd-enhancing lesions on MRI. They had lower MCP-1 levels in CSF (P<0.001) and serum (P<0.05) and higher serum levels of RANTES (P<0.05) as compared to patients without active lesions. CONCLUSIONS: MCP-1 and RANTES are differentially released during acute attacks of RR-MS, which might reflect different immunregulatory roles of these beta-chemokines in RR-MS.     

Interleukin-6 is elevated in plasma in multiple sclerosis

Levels of interleukin-6 (IL-6)--a cytokine which induces immunoglobulin production of activated B cells--were measured in cerebrospinal fluid (CSF) and plasma of patients with multiple sclerosis (MS), acute meningo-encephalitis (AM) and muscular tension headache (TH). MS patients had in repeated samples higher levels of IL-6 in plasma compared to patients with AM and TH. IL-6 concentrations in MS plasma were about 17 times higher than MS CSF, while in AM 20-fold higher levels were found in CSF compared to plasma during the acute stage. IL-6 in AM CSF decreased rapidly during clinical recovery. No correlation was found between IL-6 in MS patients' plasma or CSF and disease activity. The functional significance of elevated IL-6 concentrations in MS plasma is unknown, although the findings support the hypothesis of a systemic B cell response in MS.     

Increased reactivity to HTLV-I in inflammatory nervous system diseases

The presence of IgG antibodies reacting with purified and disrupted human T-lymphotropic virus type I (HTLV-I) was examined by an indirect enzyme-linked immunosorbent assay (ELISA) in sera from 49 patients with multiple sclerosis (MS), 21 patients with aseptic meningoencephalitis (AM), 12 patients with Guillain-Barré syndrome (GB), and 30 patients with tension headache (TH). This was also assessed in the concentrated cerebrospinal fluid (CSF) of most of these patients, as well as in sera of 60 blood donors (BD). Standardized amounts of serum IgG and CSF IgG were used in ELISA. For sera, higher reactivity with HTLV-I was found in all four patient groups compared with the BD group, but no significant differences were observed among the four groups. There was higher reactivity with HTLV-I in the CSF of patients with MS, AM, and GB compared to findings in patients with TH. Ten serum (2 MS, 3 GB, 3 TH, 2 BD) and 3 CSF (1 MS, 1 GB, 1 TH) specimens considered positive by ELISA for HTLV-I were found negative on confirmatory Western blot analysis. We extended this study to analyze the in vitro production of anti-HTLV-I-IgG antibodies by the 24-hour cultivation of unstimulated lymphocytes from peripheral blood and CSF of 6 additional patients with MS directly in HTLV-I antigen-coated wells of microtiter plates. This was followed by determination of specific antibodies by ELISA in the same wells. No antibody production was measurable. Our data do not favor the hypothesis of an HTLV-I-related human retrovirus in the etiology of MS.     

Determination of soluble ICAM-1 and TNFalphaR in the cerebrospinal fluid and serum levels in a population of Brazilian patients with relapsing-remitting multiple sclerosis

Cytokines and adhesion molecules have been implicated in the pathogenesis of multiple sclerosis (MS), a chronic inflammatory disease of the central nervous system. In this study we analyzed intrathecal (CSF) and serum levels of soluble intercellular adhesion molecule (ICAM-1) and TNFalphaR (60kD) from 20 patients with clinically definite MS during acute relapse or stable disease. Comparing to control groups of healthy individuals and patients with intervertebral herniated disc, MS patients showed increased levels (p< 0.001) of sICAM-1 and TNFalphaR in both serum and CSF samples. Regardless stage of disease there was no significant difference in the levels of sICAM-1 during acute relapse (657+/-124.9 ng/ml) or remission (627+/-36.2 ng/ml). A steady increase of TNFalphaR (60kD) in both serum and CSF, indicate the existence of a continuous inflammatory process within the brain tissue of MS patients despite absence of clinical signs of disease activity.     

Increased levels of inflammatory chemokines in amyotrophic lateral sclerosis

Background and purpose:  Amyotrophic lateral sclerosis (ALS) is classically assumed to be a neurodegenerative disorder. Inflammation has been observed in CNS tissue in ALS patients. We investigated the expression and prognostic relevance of proinflammatory chemokines in ALS.
Methods:  We analyzed nine chemokines, eotaxin, eotaxin-3, IL-8, IP-10, MCP-1, MCP-4, macrophage derived chemokine (MDC), macrophage inflammatory protein-1β (MIP-1β), and serum thymus and activation- regulated chemokine (TARC) in serum and cerebrospinal fluid (CSF) of 20 ALS- and 20 non-inflammatory neurological disease (NIND)-patients.
Results:  MCP-1 and IL-8 levels in CSF in ALS were significantly higher than in NIND (1304 pg/ml vs. 1055 pg/ml, P  = 0.013 and 22.7 pg/ml vs. 18.6 pg/ml, P  = 0.035). The expression of MCP-1 and IL-8 were higher in CSF than in serum ( P  < 0.001). There was a trend towards higher MCP-1 CSF levels in ALS patients with shorter time between first symptoms and diagnosis ( r  = −0.407; P  = 0.075).
Conclusions:  We confirmed previous findings of increased MCP-1 levels in CSF of ALS patients. Furthermore, increased levels of IL-8 in CSF suggest a stimulation of a proinflammatory cytokine cascade after microglia activation. We found a tendency for higher MCP-1 values in patients with a shorter diagnostic delay, who are known to have also a shorter survival. This may suggest an association of higher MCP-1 levels with rapidly progressing disease.     

Elevation of MCP-1 and MCP-1/VEGF ratio in cerebrospinal fluid of amyotrophic lateral sclerosis patients

Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease with progressive cell death of upper and lower motor neurons. In this study, we measured monocyte chemotactic protein-1 (MCP-1) and vascular endothelial growth factor (VEGF) levels in cerebrospinal fluid (CSF) and serum by enzyme-linked immunosorbent assay (ELISA) in 42 ALS patients, and compared these levels with those of control subjects with other neurodegenerative disorders or with those of normal controls. MCP-1 levels in CSF were significantly higher in ALS patients than in the control group. VEGF levels in CSF tended to be lower in ALS patients than in the control group, but not significantly. A positive correlation was found between MCP-1 levels in CSF of ALS patients and the total Norris scale. The elevation of MCP-1/VEGF ratio in CSF was more specific to ALS patients compared to other neurological diseases such as Parkinson's disease (PD) and spinocerebellar ataxia (SCA) and to controls. Our data suggested that both MCP-1 levels and MCP-1/VEGF ratio in CSF may be useful markers for the clinical diagnosis of ALS.     

Multiple sclerosis is associated with enhanced B cell responses to the ganglioside GD1a

The occurrence and role of autoantibodies to gangliosides and other lipid-containing components of the central nervous system in Multiple Sclerosis (MS) are unsettled. Using sensitive ELISAs, we measured IgG and IgM antibody titers and absorbances to the three major gangliosides GD1a, GD1b and GM1, and to sulfatides, cardiolipin and myelin proteins in paired serum and cerebrospinal fluid (CSF) from patients with untreated MS, optic neuritis (ON), acute aseptic meningo-encephalitis (AM) and other neurological diseases (OND). Twenty-three per cent of 30 MS (P<0.04) and 18% of 32 ON patients (P<0.05) presented elevated IgG antibody titers to GD1a in serum compared to 9% of patients with OND. Six (40%) of the patients with malignant MS had elevated serum IgG antibody titers to GD1a compared to one (6%) of the patients with benign MS (P<0.04). In CSF, elevated IgG antibody titers to GD1a were measured in 13% of MS and 20% of ON patients compared to 4% of patients with OND (P<0. 03 and P<0.02, respectively). The augmented IgG response to GD1a in serum also separated MS from Guillain-Barré syndrome. Compared to OND increased IgM absorbances to sulfatides and cardiolipin were observed in CSF of patients with MS, but also in AM. Elevated IgG antibody titers to myelin proteins were found more often in MS patients' serum and MS, ON and AM patients' CSF compared to OND. The data implicate that among the multitude of enhanced B-cell responses occurring in MS and ON, that directed to GD1a is common and more discriminative, and should be evaluated in future MS treatment studies.     

Elevation of MCP-1 and MCP-1/VEGF ratio in cerebrospinal fluid of amyotrophic lateral sclerosis patients

Abstract

Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease with progressive cell death of upper and lower motor neurons. In this study, we measured monocyte chemotactic protein-1 (MCP-1) and vascular endothelial growth factor (VEGF) levels in cerebrospinal fluid (CSF) and serum by enzyme-linked immunosorbent assay (ELISA) in 42 ALS patients, and compared these levels with those of control subjects with other neurodegenerative disorders or with those of normal controls. MCP-1 levels in CSF were significantly higher in ALS patients than in the control group. VEGF levels in CSF tended to be lower in ALS patients than in the control group, but not significantly. A positive correlation was found between MCP-1 levels in CSF of ALS patients and the total Norris scale. The elevation of MCP-1/VEGF ratio in CSF was more specific to ALS patients compared to other neurological diseases such as Parkinson's disease (PD) and spinocerebellar ataxia (SCA) and to controls. Our data suggested that both MCP-1 levels and MCP-1/VEGF ratio in CSF may be useful markers for the clinical diagnosis of ALS.