急性脑梗死患者血清IL-23/IL-17水平与颈动脉粥样硬化斑块性质的相关性研究

目的探讨急性脑梗死患者血清IL-23/IL-17水平与颈动脉粥样硬化斑块性质的相关性。方法选取85例急性脑梗死患者,按梗死体积分为小梗死灶组、中梗死灶组及大梗死灶组,按颈动脉超声检查结果分为易损斑块组、稳定斑块组及无斑块组;选取50例健康人群为对照组。对比各组血清IL-23、IL-17及C-反应蛋白(Creactive protein,CRP)水平。结果急性脑梗死组血清IL-23、IL-17、CRP水平显著高于对照组(P<0.05)。中梗死组、大梗死组患者血清IL-23、IL-17、CRP水平显著高于小梗死组(P<0.05),且中梗死组显著高于大梗死组(P<0.05)。稳定斑块组、易损斑块组患者血清IL-23、IL-17、CRP水平显著高于无斑块组(P<0.05),且易损斑块组显著高于稳定斑块组(P<0.05)。结论血清IL-23/IL-17水平可反映急性脑梗死病灶大小和颈动脉粥样硬化斑块性质。     

Effect of treatment with methylprednisolone on the serum levels of IL-12, IL-10 and CCL2 chemokine in patients with multiple sclerosis in relapse

Objectives

Interleukin-12 (IL-12), a proinflammatory cytokine produced by Th1 cells, and interleukin-10 (IL-10), a product of Th2 cells, are involved in the pathogenetic mechanisms of multiple sclerosis (MS). CCL2 chemokine expression is induced by Th2 cytokines and is decreased in MS relapse. The mechanisms responsible for the beneficial effects of IVmethylprednisolone in attacks are not clearly established and the duration of the effect of this treatment remains controversial.

Patients and methods

We measured by enzyme-like immunosorbent assay (ELISA) serum levels of IL-12, IL-10 and CCL2 before, 5 days and 1 month after the initiation of treatment with IVMP in 20 patients with MS in relapse.

Results

A significant increase of IL-10 and decrease of CCL2 serum levels was observed (p = 0.0028 and 0.045 respectively) five days after the onset of steroid treatment but not after one month. Steroid treatment had no influence in serum levels of IL-12.

Conclusions

The clinical improvement of our MS patients with relapse following the treatment with methylprednisolone may be associated with an immediate but not a long-term modification of serum levels of IL-10 and CCL2. IL-12 may not be influenced by steroid treatment.     

High levels of IL-10 secreting cells are present in blood in cerebrovascular diseases

Ischemic stroke is associated with altered systemic immune responses both early after the onset and in the recovery phase. Interleukin (IL)-10, a Th2 related cytokine, has multiple effects on different cell types, including T and B lymphocytes, monocytes, neutrophils and mast cells. IL-4 is another Th2 cytokine that inhibits the synthesis of pro-inflammatory cytokines by Th1 clones. We used enzyme-linked immunospot assays to detect and enumerate blood mononuclear cells (MNC) secreting IL-10 and IL-4 spontaneously as well as after stimulation with myelin basic protein (MBP), considered to be an autoantigen of possible pathogenic importance in, for example, multiple sclerosis, to evaluate the involvement of anti-inflammatory cytokines in ischemic stroke. All patients with ischemic stroke and cerebral hemorrhage had strongly elevated numbers of IL-10 secreting blood MNC compared with healthy individuals. Numbers of MBP-reactive IL-10 secreting blood MNC were also elevated in a proportion of the patients with stroke and hemorrhage. Levels of IL-4 secreting blood MNC did not differ in ischemic stroke versus healthy individuals. The anti-inflammatory IL-10 could play a pivotal role in ischemic stroke as well as cerebral hemorrhage.     

急性脑梗死患者血清IL-35、MMP-9与颈动脉粥样硬化斑块稳定性的关系

目的探讨急性脑梗死患者血清白细胞介素-35(IL-35)、基质金属蛋白酶9(MMP-9)与颈动脉粥样硬化斑块稳定性的关系。方法选择急性脑梗死患者89例,应用彩色多普勒超声检查颈动脉斑块,根据颈动脉粥样硬化斑块稳定性分为易损斑块组和稳定斑块组。采用酶联免疫吸附法检测患者血清IL-35、MMP-9水平,并分析IL-35、MMP-9与斑块稳定性的关系。结果颈动脉粥样硬化易损斑块组的患者41例,稳定斑块组的患者48例。易损斑块组血清IL-35水平(17.89±7.21 ng/ml)明显高于稳定斑块组(9.08±3.45 ng/ml)(P<0.05)。MMP-9水平易损斑块组(430.36±72.78 ng/ml)亦显著高于稳定斑块组(305.16±45.63 ng/ml)(P<0.01),差异均有统计学意义。结论脑梗死患者血清IL-35、MMP-9水平可能与颈动脉斑块稳定性有关。     

急性脑梗死患者血清白细胞介素-18和基质金属蛋白酶-9水平及其临床意义

目的探讨急性脑梗死患者血清白细胞介素-18(IL-18)和基质金属蛋白酶-9(MMP-9)水平的变化及其临床意义。方法 53例急性脑梗死患者,根据脑梗死体积和临床神经功能缺损程度评分分组。采用酶联免疫吸附法(ELISA)检测血清IL-18和MMP-9水平并与正常对照组比较。应用SPSS 13.0版统计软件进行分析。结果急性脑梗死患者血清IL-18和MMP-9水平明显高于正常对照组(P<0.01),大梗死组患者血清IL-18和MMP-9水平高于小梗死组(P<0.05),患者血清IL-18和MMP-9水平与脑梗死体积呈正相关(P<0.05);轻型组、中型组、重型组患者血清IL-18和MMP-9水平依次升高,各组之间差异有统计学意义(P<0.05),患者血清IL-18和MMP-9水平与临床神经功能缺损程度评分呈正相关(P<0.05)。结论急性脑梗死患者血清IL-18和MMP-9水平升高;血清IL–18和MMP-9水平与脑梗死体积及临床神经功能缺损程度相关,检测其水平有助于判断急性脑梗死患者的病情及预后。     

Monocytic, Th1 and th2 cytokine alterations in the pathophysiology of schizophrenia

A growing body of evidence suggests that changes in the serum levels and cellular production of various cytokines are associated with the immunological abnormalities of schizophrenia. Several studies have examined alterations in T helper type 1 (Th1) and T helper type 2 (Th2) cytokines in schizophrenia. We explored monocytic, Th1 and Th2 cytokines in 43 schizophrenia patients and 50 normal controls. The mitogen-induced production of tumor necrosis factor alpha (TNF-alpha), interleukin 6 (IL-6), IL-4, gamma-interferon (IFN-gamma) and IL-2 was measured with enzyme-linked immunosorbent assays before and after antipsychotic treatment. IL-6 and TNF-alpha production by schizophrenic patients was significantly higher than by normal controls, while IL-2, IL-4 and IFN-gamma production was significantly lower in schizophrenic patients. After 6 weeks of antipsychotic treatment, IL-6 and TNF-alpha production was significantly decreased, while IL-4, IFN-gamma and IL-2 productions were not significantly changed. Our results suggest that increased monocytic cytokines and decreased Th1 and Th2 cytokines may be associated with the immunopathogenesis of acute psychotic schizophrenia, and that antipsychotics may play an important role in immune response by decreasing elevated monocytic cytokines.     

Increased intrathecal TGF-β1, but not IL-12, IFN-γ and IL-10 levels in Alzheimer’s disease patients

Abstract An inflammatory response has been hypothesised to be involved in the pathogenesis of primary dementias, above all Alzheimer’s disease (AD). This study was aimed at evaluating interleukin (IL)-12 and a panel of related cytokine levels in paired CSF and sera of demented patients. IL-12 (p70 heterodimer and total IL-12 p40 chain), interferon (IFN)-γ, IL-10 and transforming growth factor (TGF)-β1 levels were measured in 30 patients with probable Alzheimer’s disease (PrAD), 57 patients with other dementing disorders, including probable vascular dementia (PrVD), Parkinson’s disease (PD) and normal pressure hydrocephalus (NPH), and 25 cognitively normal control subjects. In the presence of unchanged concentrations of IL-12, IFN-γ and IL-10, the mean CSF level of TGF-β1 and the correspondent TGF-β1 index, but not the serum level, were significantly increased in PrAD compared to controls and PrVD, whereas no difference was found vs. NPH and PD. Our results support the pathophysiological role of TGF-β1 system in AD.     

Elevated circulating levels of IL-6 in schizophrenia

Schizophrenia may result from immune or inflammatory disorders, which are mediated by cytokines. Data in this field are heterogeneous and often contradictory. We investigated circulating levels of IL-6 and TNF-α, two distinct proinflammatory cytokines. Using immunoassay, we assessed IL-6 and TNF-α in serum from chronic schizophrenic patients (n=30) and normal controls (n=15). Circulating levels of IL-6 were higher in patients than in controls; those of TNF-α were not significantly higher than in controls. In addition, IL-6 levels were higher in patients with acute exacerbation of schizophrenia than in patients with remissions. Our results suggest that immunologic abnormalities in schizophrenia may be related to a specific inflammatory process mediated by IL-6. An interesting line of research would be the evaluation of IL-6 cerebral production in CSF.     

脑梗死患者血清IL-6含量动态变化研究

目的 研究脑梗死患者血清ＩＬ－６含量变化及其意义。方法 我们用双抗体夹心ＥＬＩＳ地３０例糖梗死患者的表分别在发病１ｄ、３ｄ、７ｄ进行了连续检测，并用２０例健康人们作对照。结果 发现脑梗死患者血清ＩＬ－６含量在３个时间点均高于对照组（Ｐ〈０．０５），在病程第１天血清ＩＬ－６含量高于第３天第７天（Ｐ〈０．０５），且大面积脑梗死组血清ＩＬ－６含量高于小面积脑梗死组，神经功能受损重者血清ＩＬ－６含量高于神     

Effects of interferon-beta therapy on innate and adaptive immune responses to the human endogenous retroviruses HERV-H and HERV-W, cytokine production, and the lectin complement activation pathway in multiple sclerosis

The effects of treatment of multiple sclerosis patients with IFN-β on elements in the innate and adaptive immune response were analysed in a longitudinal study. We demonstrate significant decreases in anti-Envelope antibody reactivity for the two closely related Gammaretroviral human endogenous retroviruses (HERVs), HERV-H and HERV-W, as a consequence of IFN-β therapy, closely linked to efficacy of therapy/low disease activity. We also show strong indications of a protective effect of high levels of two components in the innate pathogen-associated molecular pattern recognition: mannan-binding lectin (MBL), and MBL-associated serine protease 3 (MASP-3).Serum levels of typical Th1- and Th2-related, MS-relevant cytokines were also monitored. Overall both Th1- and Th2-associated cytokines were modestly, albeit significantly up-regulated, notably IL-2 and TNF-α (MS patients with inactive disease), as well as IL-4 and, to some extent IL-10 (no increase in IL-10 for MS patients with active disease (non-responders)). We found no overall changes in Th1/Th2 ratios.Our results support that HERV-H/HERV-W and the antiviral immune response may play a role in MS development, and that these HERVs have potential as biomarkers for disease activity.     

人脑缺血组织中IL-17表达及来源

目的证实IL-17是否参与人脑缺血损伤过程以及缺血脑组织中表达IL-17细胞的来源。方法选择疾病不同时间,尸检取因脑梗死死亡人的脑组织,以对侧正常脑组织为对照,通过免疫组织化学方法检测IL-17在人类脑组织中的表达。用线栓法封闭SD大鼠右侧大脑中动脉制作pMCAO动物模型。寡核苷酸原位杂交检测脑缺血不同时间点IL-17的表达;利用GFAP抗体和IL-17抗体双染方法检测大鼠脑组织中GFAP、IL-17共同表达细胞-神经胶质细胞。结果人脑缺血病灶中IL-17呈高表达,与对照侧脑组织相比存在极显著差异。IL-17表达高峰在发病后3~5d。SD大鼠缺血侧脑组织IL-17表达6h开始增高(P<0.01),第6天达到高峰。pMCAO手术侧可见大量IL-17和GFAP双染细胞。结论IL-17参与了人类及大鼠脑组织缺血性损伤的局部炎症反应过程;在大鼠实验中证实IL-17表达细胞来源于除以往确认的T淋巴细胞外,还包括神经胶质细胞。     

脑卒中急性期血清白介素-10和外周血T淋巴细胞Ag-NORs的动态变化

目的 研究脑卒中急性期血清IL-10的动态变化规律以及细胞免疫功能变化.方法 选择3 d内首次发病患者,IL-10采用ELISA方法于发病72 h内、第6～8天及第14～15天抽血检测,Ag-NORs于发病72 h内、第14～15天抽血,对外周血T淋巴细胞染色分析,以核仁银染面积与细胞核面积比值（I.S%）作为Ag-NORs检测指标,对照组抽血检测1次.结果 脑卒中组血清IL-10水平各时间点均较对照组明显增高（P＜0.05）,不同时间无明显变化（P＞0.05）,不同病情亦无明显差异（P＞0.05）.脑卒中患者急性期Ag-NORs水平（I.S%）明显降低（P＜0.01）,发病后第14～15 d较72 h内高（P＜0.01）,但仍低于对照组（P＜0.01）.脑梗死组同一时期重度患者Ag-NORs水平较轻度患者低（P＜0.05）.结论 IL-10在脑卒中急性期明显增高,参与了卒中炎性损伤的病理过程,有望成为治疗脑卒中的潜在药物.且脑卒中急性期细胞免疫功能低下.     

DPB 1 *0501-associated opticomyelitis and atopic myelitis: novel disease entities]

To clarify the relationship between Th 1/Th 2 balance and clinical features, we studied the intracellular IFN gamma-positive versus IL-4-positive cell ratio in peripheral blood CD 4 T cells by flow cytometry and measured total and allergen-specific IgE by ELISA in 227 patients with various neurologic diseases including multiple sclerosis (MS), myelitis and HAM/TSP, and 42 healthy hospital subjects. The intracellular IFN gamma/IL-4 ratio in the patients with acute myelitis was significantly decreased, and the total serum IgE level and frequency of mite antigen-specific IgE were significantly elevated as compared with the controls. Patients with HAM/TSP, however, had a significantly higher intracellular IFN gamma/IL-4 ratio, lower total IgE level, and lower frequency of cedar pollen-specific IgE than did the controls. The patients with recurrent opticomyelitis (ROM) had a significantly higher frequency of relapse, higher EDSS score, and lower number of brain MRI lesions than the patients with conventional MS, and only those with ROM showed a significant association with the HLA-DPB 1 *0501 allele. The ROM patients had a significantly higher intracellular IFN gamma/IL-4 ratio and IL-4-/IFN-gamma + cell percentages than the controls. These findings suggest that the Th 2 cell response predominates in acute myelitis with hyperIgEaemia (atopic myelitis), whereas the Th 1 cell response predominates in ROM and HAM/TSP.     

Correlations between IL-4, IL-12 levels and CCL2, CCL5 levels in serum and cerebrospinal fluid of multiple sclerosis patients

Summary. Multiple sclerosis (MS) is an inflammatory disease of the central nervous system (CNS). Both cytokines and chemokines have been implicated in the pathogenesis of MS. The aim of the study was to assess whether cytokine levels are correlated with chemokine levels during a different stage of relapsing-remitting MS (RR-MS). The study included 53 patients with RR-MS (20 subjects in stable stage and 18 patients with relapse). By ELISA method, the levels of the interleukin-4 (IL-4), interleukin-12 (IL-12), CCL2 and CCL-5 chemokines were measured both in serum and cerebrospinal fluid (CSF) of all patients. The serum IL-4 and IL-12 levels and CSF CCL5 level of patients with stable RR-MS were significantly different from the control level and the IL-12 levels were correlated with CCL5 levels in serum. During the relapse, a significant change in chemokine levels both in serum and CSF and IL-12 in CSF were noted, however no correlations were found between cytokines and chemokines.     

急性脑梗死与炎症的关系探讨

目的通过测定急性脑梗死患者血清中炎症标记物白细胞介素-6(interleukin-6,IL-6)、C反应蛋白(C-reactive protein,CRP)含量,探讨其生化指标在急性脑梗死临床诊治中的应用前景及炎症与脑梗死的关系。方法测定60例急性脑梗死患者不同时期及60例健康对照者血清IL-6、CRP含量及NIHSS评分分析炎症与脑梗死的关系。结果血清IL-6、CRP含量在急性脑梗死后逐渐增加,72h达高峰,急性脑梗死患者血清IL-6、CRP含量明显高于对照组(P均0.01)。结论炎症反应可能参与了急性脑梗死的发生,血清高水平IL-6、CRP有望用于预测脑梗死的预后。     

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.     

Th1 dominance in HAM/TSP and the optico-spinal form of multiple sclerosis versus Th2 dominance in mite antigen-specific IgE myelitis

To clarify the Th1/Th2 balance in spinal cord inflammation, we used ELISA to measure the total and allergen-specific IgE in 69 patients with clinically definite multiple sclerosis (MS), including 24 patients with the optico-spinal form of MS, 45 with HAM/TSP, 30 HTLV-I carriers without HAM/TSP, 40 patients with acute myelitis, 43 with neurodegenerative disorders, and 42 healthy subjects, and flow cytometry to study the intracellular IFNgamma-positive versus IL-4-positive cell ratio (intracellular IFNgamma/IL-4 ratio) in peripheral blood CD4(+) T cells in 40 patients with MS, including 17 patients with the optico-spinal form of MS, 23 with HAM/TSP, 22 with acute myelitis, 23 with neurodegenerative disorders, and 36 healthy subjects. Patients with HAM/TSP showed a significantly higher intracellular IFNgamma/IL-4 ratio, lower IL-4(+)/IFN-gamma(-) cell percentages, lower total IgE level, and lower frequency of cedar pollen-specific IgE than did the controls. The patients with optico-spinal MS showed a significantly higher intracellular IFNgamma/IL-4 ratio and higher IL-4(-)/IFN-gamma(+) cell percentages than the controls even at remission or in the convalescence phase. In contrast, in the patients with acute myelitis, the total serum IgE level and the frequency of mite antigen-specific IgE were significantly elevated in comparison to the controls, while those having mite antigen-specific IgE myelitis showed a significantly lower IFNgamma/IL-4 ratio in the CD4(+) T cells in comparison to the controls. These findings suggest that the Th1 cell response is predominant in HAM/TSP and optico-spinal MS, whereas the Th2 cell response is predominant in mite antigen-specific IgE myelitis.     

Membrane bound IL-15 is increased on CD14 monocytes in early stages of MS

IL-15 is a pro-inflammatory cytokine whose three-dimensional structure is similar to that of IL-2. IL-2 and IL-15 have similar as well as distinct biological functions. An active form of IL-15 that is membrane bound has also been described. Furthermore, IL-15 is known to play a role in autoimmune diseases. We thus investigated the expression of membrane bound IL-15 on monocytes (CD14+ cells) and studied its effect on T cell activation in MS patients. We found that unstimulated CD14+ cells from relapsing remitting MS patients had increased membrane bound IL-15. Those with high surface levels of IL-15 on monocytes were in the early stages of the disease. In addition, we found that T cells of MS patients had enhanced responsiveness to IL-15 and there was increased expression of IL-15 receptor on CD4+ T cells. Thus, IL-15 may be an important cytokine that drives Th1 responses early in the course of the disease and could serve as a target for immunotherapy and as an early marker in the immunologic staging of MS.     

颅脑损伤后血清TNF-α和IL-10的含量变化及意义

目的 探讨急性颅脑损伤后血清肿瘤坏死因子α（TNF-α）和白细胞介素10（IL-10）的含量变化及临床意义。方法 采用双抗体夹心ABC-ELISA方法,检测60例急性颅脑损伤患者伤后血清TNF-α和IL-10含量的变化。结果 TNF-α、IL-10在伤后早期即明显升高,并与伤情轻重呈正相关。结论 TNF-α和IL-10参与了急性颅脑损伤后的炎性反应过程,血清中TNF-α和IL-10含量在颅脑损伤后明显升高,与颅脑损伤程度呈正相关,并可能在继发性脑损害中起重要作用。     

急性脑梗死患者血清IL-18含量动态变化研究

目的动态观察急性脑梗死患者血清白介素-18(Interleukin-18,IL-18)含量变化,探讨炎症因子在脑梗死发病机制中的作用。方法选取46例急性脑梗死患者发病1d、3d、7d和14d时的空腹静脉血,采用双抗体夹心酶联免疫吸附法(ELISA)测定血清IL-18的水平,并与30名健康对照组比较。结果急性脑梗死患者发病1d内、3d、7d和14d时血清IL-18水平均显著高于正常对照组(P<0.05),其中发病3d水平最高,随时间推移及治疗的介入,炎症因子水平逐渐下降;3d测定的不同梗死体积患者血清IL-18含量存在显著性差异(P<0.05)。结论急性脑梗死患者血清IL-18水平明显升高,并与急性脑梗死的体积密切相关,对炎症反应的干预治疗可能有利于减轻缺血性脑损害。