精神分裂症患者的干扰素及白介素表达水平的研究

目的:分析精神分裂症患者外周血单个核细胞(PBMCs)IFN-γ、IL-12、IL-18的表达水平，从细胞因子水平探讨精神分裂症患者的免疫功能状况。方法：用酶联免疫法(ELISA)检测34例精神分裂症患者和20例正常人PBMCs IFN-γ、IL-12、IL-18的表达水平。结果：精神分裂症患者PBMCs的IFN-γ、IL-12、IL-18的表达水平比正常人显著增高。结论：PBMCs的IFN-γ、IL-12、IL-18的表达增强，提示精神分裂症患者免疫功能混乱。     

IL-12和IL-18的体外联合孵育协同增强P0180-199T/Th1细胞增殖和分化的实验研究

目的 研究IL-12和IL-18是否能够协同增强P0180-199T／Th1淋巴细胞的增殖和分化。方法 用IL-12和／或IL-18体外孵育的P0180-199T细胞过继免疫正常动物，引发AT-EAN后，用流式细胞仪检测单独组和联合组的脾T淋巴细胞的增殖，ELISA法检测单独组和联合组的细胞培养上清和血清中Th1和Th2细胞因子的变化。结果 与IL-12组或IL-18组比较，IL-12和IL-18的联合孵育使P0180-199T细胞的CD4^-T／Th1分化能力增强．表现为脾细胞的CD4^-／CD8^-的比值显著上调，细胞培养上清和AT-EAN血清中IFN-γ的显著上调．具有显著性差异。结论 IL-12和IL-18能够协同增强P0180-199T／Th1淋巴细胞的增殖和分化。     

血清炎性细胞因子IL-1α、IL-6、IL-12、CRP水平与首发广泛性焦虑障碍发病相关性及作用机制分析

目的探讨首发广泛性焦虑障碍患者外周血炎性细胞因子IL-1α、IL-6、IL-12、CRP变化与焦虑症状和执行功能的相关性。方法选取我院2016年5月～2017年5月确诊的首发广泛性焦虑障碍患者100例,本院健康对象50例作为对照组。检测血清中炎性细胞因子IL-1α、IL-6、IL-12、CRP的水平,评估焦虑水平、总体焦虑程度和特质焦虑、状态焦虑水平,测定执行功能。结果首发广泛性焦虑障碍组IL-1α、IL-6、IL-12、CRP等炎性细胞因子水平显著高于正常对照组(P0.05);状态焦虑SAI、特质焦虑TAI与IL-1α、IL-6、IL-12均呈显著正相关;外维转换错误数与外周血IL-1α、IL-6、IL-12、CRP水平呈正相关。结论首发广泛性焦虑障碍患者存在炎性细胞因子和执行功能异常,和总体焦虑程度、状态焦虑及特质焦虑水平呈正相关。     

多基因修饰的胶质瘤细胞接种后机体免疫功能的变化

目的研究如何提高胶质瘤细胞的免疫原性,探讨胶质瘤免疫治疗的新途径。方法用重组腺病毒作载体,将共刺激分子B7-1基因和具有多重免疫功能的IL-2基因转入G422小鼠胶质母细胞瘤细胞中,取1×105个细胞(体积0.1ml),在小鼠皮下接种,分野生型对照组、lacZ组、IL-2组、B7-1组和B7-1+IL-2组。接种后不同时间测量肿瘤大小。两周后检测荷瘤小鼠脾细胞的NK、LAK和CTL的活性及细胞因子的分泌。结果B7-1+IL-2组肿瘤生长明显受抑制(P<0.05)。B7-1组的NK、LAK、CTL的杀伤活性及脾细胞分泌细胞因子的水平都很低,与对照组相差不显著。IL-2组的CTL的杀伤活性较高,与对照组相差显著(P<0.05),而NK和LAK活性及细胞因子水平与对照组相差不显著。B7-1+IL-2组的NK、LAK、CTL和脾细胞分泌细胞因子的活性与对照组相比,相差都非常显著(P<0.01)。结论单纯B7-1基因转染G422细胞不能增强其免疫原性;IL-2基因转染后,对机体的免疫反应有一定的增强作用,但效果不够理想;B7-1基因和IL-2基因联合转染G422细胞则可以明显增强其免疫原性,并有效激活荷瘤小鼠的特异性抗肿瘤免疫反应。     

新生儿缺氧缺血性脑病血清细胞因子的变化及意义

目的 探讨新生儿缺氧缺血性脑病患儿血清细胞因子的水平变化及意义.方法 选择46例新生儿缺氧缺血性脑病为病例组,根据病情分为轻度组(21例)、中度组(13例)和重度组(12例),选择同期在我院正常分娩的新生儿40例为对照组,ELISA法检测血清肿瘤坏死因子-α(tumor necrosis factor-α,TNF-α)、白介素-6(interleukin-6,IL-6)和白介素-18(interleukin-18,IL-18)水平.结果 病例组患儿血清TNF-α、IL-6和IL-18水平均高于对照组,差异有统计学意义(P<0.05),且重度组患儿上述细胞因子水平高于中度组和轻度组,而中度组患儿上述细胞因子水平高于轻度组,差异有统计学意义(P<0.05);病例组患儿血清TNF-α与IL-6、IL-18均呈正相关(r分别为0.489和0.452),IL-6与IL-18也均呈正相关(r=0.426),差异均有统计学意义(P<0.05).结论 TNF-α、IL-6和IL-18等细胞因子相互作用,共同参与新生儿缺氧缺血性脑病的病理过程,其血清水平与病情程度存在一定关系.     

帕金森病患者外周血Th1/Th2类细胞因子的基因表达

目的 探讨细胞因子在帕金森病（PD）发病机制中的作用。方法 对26例初诊未经治疗的原发性PD患者（PD1）,27例经左旋多巴、美多巴治疗的PD患者（PD2）及30名年龄、性别相匹配的健康对照者,于清晨抽静脉血5ml,梯度离心分离外周血单核细胞（PBMC）后,采用逆转录聚合酶链反应（RT-PCR）技术,分别检测各组PBMC中白细胞介素-2（IL-2）、1干扰素（INF-1）、IL-4、IL-6、IL-10细胞因子信使核糖核酸（mRNA）的表达。结果 PD患者外周血单核细胞IL-6基因表达增强（P〈0.05）。PD组PMBC中IL-2、IFN-1、IL-4、IL-104种细胞因子基因的表达与对照组相比差异无显著性（均P〉0,05）。PD2组与PD1组比较,所测PMBC中5种细胞因子基因的表达虽均有所下降,但差异无显著性。结论 PD患者PBMC存在辅助性T细胞（Th2）漂移倾向,表明免疫机制在PD的发病中具有重要作用。     

78例首发精神分裂症患者细胞因子的研究

目的探讨细胞因子在精神分裂症病理、生理机制中的作用。方法采用放射免疫法对78例首发精神分裂症患者和35名正常人的血浆白细胞介素1β（IL-1β）、白细胞介素2（IL-2）、白细胞介素6（IL-6）、白细胞介素8（IL-8）、α-肿瘤坏死因子（TNFα）进行检测,同时用阳性与阴性症状量表（PANSS）评定精神分裂症患者精神症状。结果精神分裂症患者血浆IL-1β、IL-6、IL-8、TNFα水平均显著高于正常对照组,IL-2显著低于正常对照组。结论提示精神分裂症患者的免疫功能处于亢进状态,细胞因子与精神病理之间有着一定关系。     

IL-33及其在中枢神经系统中作用的研究进展(英文)

白介素-33(interleukin-33,IL-33)是IL-1家族的新成员,在多种细胞和组织中表达。IL-33能与常染色体结合,因此被认为具有抑制核内转录的作用。当受到炎性刺激时,IL-33可作为危险信号的警报释放到细胞外发挥细胞因子的作用。IL-33的受体是由ST2和IL-1受体结合蛋白组成的异物二聚体,其中IL-1受体结合蛋白是所有白介素家族受体共有的部分。IL-33/ST2信号通路通过调节细胞因子的生成,不仅对炎症、免疫性疾病发挥关键作用,还参与了许多其他疾病如中枢神经系统疾病。近年来有关IL-33尤其是它在中枢神经系统中表达及功能的研究不断增多,本文对IL-33及其在中枢神经系统中的作用进行了综述。     

多奈哌齐治疗老年性痴呆的临床研究

目的:探讨乙酰胆碱和促炎症细胞因子在AD发病机制中的相互关系。方法:采用对照研究,对36名阿尔茨海默病(Alzheimer’sdisease,AD)患者用MMSE量表测定其治疗前后认知功能;采用Elisa方法测定乙酰胆碱酯酶抑制剂治疗前后脑脊液中白介素-1、肿瘤坏死因子、白介素-6等细胞因子的变化。结果:多奈哌齐组治疗24周后认知功能与治疗前比较明显提高,认知功能改善比脑复康组明显,同时CSF中IL-1、TNF-α、IL-6和sIL-6R的水平与治疗前相比,均明显降低且有显著意义(P<0.01)。结论:胆碱酯酶抑制剂多奈哌齐治疗AD,改善认知功能的同时,可使脑内促炎症细胞因子有所降低。提示胆碱能功能与促炎症细胞因子在AD发病中相互影响,具有密切联系。     

重症肌无力患者血清Th1/Th2/Th17细胞因子的变化及意义

目的：分析重症肌无力（MG）患者血清CD4^＋ T细胞主要细胞因子的水平,探讨不同亚型CD4^＋ T细胞分泌的细胞因子在MG发病机制中的作用。方法：用ELISA测定93例MG患者和34名健康对照者血清中各项细胞因子（IL-2、IL-12、IFN-γ、TNF-α、IL-4、IL-10、IL-13和IL-17）的水平,分组行统计学分析。结果：与健康对照组相比,MG患者Th1细胞相关各细胞因子（IL-2、IL-12、IFN-γ及TNF-α）均明显升高,差异有统计学意义（P〈0.05）;Th2细胞相关的细胞因子IL-4、IL-10差异无统计学意义（P〉0.05）,仅IL-13水平升高;Th17细胞的细胞因子IL-17水平差异无统计学意义（P〉0.05）。MG眼肌型与全身型患者血清中各细胞因子水平的差异无统计学意义（P〉0.05）,在不同病程的MG患者中差异也无统计学意义（P〉0.05）。结论：Th1细胞因子在MG发病机制中发挥重要作用,而Th2细胞及其细胞因子在MG机制中的角色各异。     

Role of hormone-controlled Th1- and Th2-type cytokines in successful pregnancy

Development of CD4+ helper T (Th) cells into type 1 (Th1) or type 2 (Th2) effectors, as characterized by their opposite pattern of cytokine production, can be influenced by several factors, including hormones. Progesterone promotes the production of IL-4 and IL-5, whereas relaxin promotes the production of IFN-gamma by T cells. Leukemia inhibitory factor (LIF), essential for embryo implantation, is up-regulated by IL-4 and progesterone. Moreover, the production of LIF and/or Th2 cytokines by decidual T cells contributes to the maintenance of pregnancy. Our results suggest that relaxin and progesterone may contribute to the regulation of the immune homeostasis during pregnancy.     

Serum interleukin-18 levels are elevated in schizophrenia

Interleukin-18 (IL-18) is a recently discovered proinflammatory cytokine which plays a pivotal role in T helper 1 (Th1) responses. IL-18 is produced by macrophage-like cells, and inappropriate IL-18 production has been known to be involved in immunological disturbances. Schizophrenia is a common disease whose pathogenesis is still unclear; however, an activation of the inflammatory response system, including the Th1 cytokine response, may be related to the pathophysiology of schizophrenia. We measured the serum IL-18 levels of 66 schizophrenics and age- and sex-matched control subjects by using an ELISA assay. We found significantly increased serum IL-18 levels in the schizophrenic patients (P=0.0002). This finding supports the hypothesis that immune activation is involved in the pathophysiology of schizophrenia.     

Pentoxifylline, a phosphodiesterase inhibitor, induces immune deviation in patients with multiple sclerosis

The outcome of immune responses can be predicted by the lymphokine production pattern of the participating cells. Cytokines of the T helper type 1 (Th1) cells mediate inflammatory responses and delayed-type hypersensitivity (DTH), whereas Th2-like T cells predominantly produce cytokines, which stimulate antibody production by B cells. Immunoregulatory therapy of autoimmune diseases with unknown antigens may be achieved by inhibiting the production of inflammatory cytokines and induction of protective cytokines of Th2-like T cells. To determine the immunoregulatory capacity of the phosphodiesterase inhibitor pentoxifylline (PTX), which is known to suppress the production of tumor necrosis factor-alpha (TNF-α) and interferon-gamma (IFN-γ), this drug was used in mitogen and antigen-stimulated lymphocyte cultures as well as in patients with multiple sclerosis. PTX significantly decreased TNF-α and interleukin-12 (IL-12), whereas it increased IL-4 and IL-10 production. In addition, PTX inhibited cell proliferation, which was associated with a marked reduction in CD25 (IL-2 receptor α-chain) and CDS4 (intercellular adhesion molecule-1; ICAM-1) expression. Increasing doses of PTX significantly reduced TNF-α and IL-12 mRNA expression of blood mononuclear cells, but increased IL-4 and IL-10 expression in eight patients with relapsing-remitting multiple sclerosis. These results indicate that PTX modulates immune reactions favouring a Th2-like response and may therefore be useful for the treatment of autoimmune diseases with a dominant Th1-like T cell response.     

Prolactin in autoimmunity and antitumor defence

Prolactin (PRL) enhances inflammatory and antitumor responses in vitro and thus exhibits Th1-type cytokine-like effects. Evidence from experimental models indicates that inhibition of PRL release by bromocriptine downregulates immune reactions and ameliorates autoimmune diseases in which Th1 responses are predominant. A direct effect of locally produced PRL in some Th1 diseases, such as rheumatoid arthritis, supports this concept. Paradoxically, however, hyperprolactinemia can also be associated with conditions such as pregnancy, where remission of Th1-mediated diseases is known to occur in the context of a Th2-dominated milieu. This reversal of the Th1-promoting effect of PRL may be due to major changes in the levels of other hormones that can annul and/or override the PRL-mediated proinflammatory state. Nevertheless, PRL, as an immunopotentiating agent, may have a powerful therapeutic role in cancer and other immunocompromised patients.     

TH1/TH2 cytokines in the central nervous system

For the past 20 years it has become increasingly evident that cytokines play an important role in both the normal development of the brain, acting as neurotrophic factors, and in brain injuries. Although cytokines and their receptors are synthesized and expressed in the brain (normally at low levels), increased cytokine production levels are now associated with various neurological disorders. T lymphocytes are the cells responsible for coordinating the immune response and a major source of cytokines. Different cytokines induce different subsets of T cells or have different effects on proliferation within a particular subset. Recent studies suggest that the immune response is in fact regulated by the balance between Th1 and Th2 cytokines. These two pathways are often mutually exclusive, the one resulting in protection and the other in progression of disease. Various studies describe the function and production of proinflammatory cytokines in the central nervous system (CNS) and their role in health and disease. Inflammation is upregulated following activation of Th1 cells, whereas Th2 cells may play a significant role in downregulating Th1 proinflammatory responses in those instances in which there is overproduction of Th2 cytokines. Although both Th1 and Th2 cytokines may influence CNS functioning, most studies have so far dealt with proinflammatory cytokines, probably because they directly affect CNS cells and are thought to be implicated in CNS pathology. It is of interest that endogenous glucocorticoids also control Th1-Th2 balance, favoring Th2 cell development. This review presents the evidence that cytokines have important functions in the CNS, both during development and as a part of brain pathology. In particular, the author highlighted recent work that supports a major role for the so-called inflammatory cytokines, Th1, and the anti-inflammatory Th2 cytokines.     

In vitro recovery of Th1/Th2 balance in PBMCs from patients with immune thrombocytopenia through the actions of IL-18BPa/Fc

To determine the effects of IL-18BPa/Fc on the cytokine production and survival of peripheral blood mononuclear cells (PBMCs) of immune thrombocytopenia (ITP), PBMCs isolated from patients with ITP and healthy donors were treated with or without of IL-18BPa/Fc. The production of IFN-γ, IL-2, tumor necrosis factor (TNF)-α, IL-4, IL-5 and IL-10 was measured by ELISA, and mRNA expression of IFN-γ and IL-18R was evaluated by RT-PCR. Besides, flow cytometric analysis of cell apoptosis was performed by staining with annexin V-FITC/ Propidium Iodide (PI). The proliferation rate of PBMCs was examined by CCK-8 assay. IL-18BPa/Fc at 10 ng/ml significantly stimulated IL-10 secretion from PBMCs in patients with ITP and healthy donors, while it decreased IFN-γ release. Further, IL-18BPa/Fc enhanced dexamethason(DEX) reduction of PHA-induced IFN-γ production by an additional 38.9%(DEX 20 nmol/l) and 49.9%(DEX 50 nmol/l) in ITP patients. Interestingly, the treatment of PBMCs with IL-18BPa/Fc increased the percentage of early apoptotic cells in patients with ITP. In conclusion, IL-18BPa/Fc, via neutralizing the biologic activity of mature IL-18, accelerates lymphocyte apoptosis and downregulates IFN-γ, while permitting the production of Th2 cytokine IL-10. These observations suggest a role of IL-18BPa/Fc in the recovery of Th1/Th2 balance, as well as its therapeutic potential in the treatment of ITP.     

Organizational strategy use in obsessive-compulsive disorder

It has been reported that the balance between T-helper type 1 (Th1) cytokines and T-helper type 2 (Th2) cytokines plays a role in psychiatric disorders such as bipolar disorder. The T-helper type 3 (Th3) cytokine, which transforming growth factor beta-1 (TGF-β1), has been shown to modulate the production of Th1 and Th2 cytokines. However, the role of TGF-β1 in bipolar disorder has not yet been explored. A total of 70 manic patients with bipolar disorder and 96 normal controls was recruited. The plasma levels of IFN-γ, IL-4, and TGF-β1 were studied at the time of admission and 8 weeks after mood stabilizer treatment. The detection rate and plasma concentrations of IFN-γ and IL-4 and the IFN-γ/TGF-β1 and IL-4/TGF-β1 ratios were significantly higher in patients than in controls, while the TGF-β1 level was significantly lower. The TGF-β1 level increased significantly after treatment and the IFN-γ/TGF-β1 and IL-4/TGF-β1 ratios returned to control values. TGF-β1 may play a role in the pathophysiology of bipolar disorder through the action of TGF-β1 in modulating the IL-4/TGF-β1 ratio.     

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.     

Amelioration of Experimental Autoimmune Encephalomyelitis by β-elemene Treatment is Associated with Th17 and Treg Cell Balance

Experimental autoimmune encephalomyelitis (EAE), an animal mode of multiple sclerosis (MS), was previously considered that is mediated by Th1 cells. However, a number of recent studies provided strong evidence that T helper cells that produce interleukin (IL)-17 (Th17) and anti-inflammatory CD4+ Foxp3+ regulatory T cells (Tregs) play a dominant role in the pathogenesis of EAE. β-elemene is a natural antitumor plant drug with the role of multiple target, and it has been found to pass through the blood–brain barrier easily. It also has been strongly implicated as an immune modulatory agent, but the precise mechanisms of its action are largely unknown. In the present study, we mainly investigated the efficacy and mechanism of β-elemene against EAE in vivo and vitro. The treatment of C57 mice with β-elemene significantly delayed the onset of EAE, markedly suppressed MOG-specific T cell proliferation in a dose-dependent manner, dramatically reduced the IL-17, IL-6, IL-23, and RORγt production and induced the Foxp3 expression in both the periphery and the inflamed spinal cord. These findings indicated that β-elemene amelioration EAE was, to a large extent, due to inhibit differentiation and development of Th17 cells depends on down-regulating expression of IL-6, IL-23, RORγt signaling, and promoting expansion in Treg cells. Suggesting it is useful in the control of MS and other Th17 cell-mediated inflammatory diseases.     

Neonatal induction of myelin-specific Th1/Th17 immunity does not result in experimental autoimmune encephalomyelitis and can protect against the disease in adulthood

The neonatal immune system is believed to be biased towards T helper type 2 (Th2) immunity, but under certain conditions neonates can also develop Th1 immune responses. Neonatal Th2 immunity to myelin antigens is not pathogenic and can prevent induction of experimental autoimmune encephalomyelitis (EAE) in adulthood, but the consequences of neonatally induced Th1 immunity to self-antigens have remained unresolved. Here, we show that neonatal injection of mice with myelin antigens emulsified in complete Freund's adjuvant (CFA) induced vigorous production of IFN-gamma and IL-17, but not IL-5, consistent with myelin-specific Th1/Th17 immunity. Importantly, the myelin-specific Th1/Th17 cells persisted in the mice until adulthood without causing symptoms of EAE. Intraperitoneal, but not subcutaneous injection of neonates with myelin antigens protected against induction of EAE as adults. Intraperitoneally injected neonates showed a substantial decrease of the number and avidity of myelin-reactive Th17 cells, suggesting a decrease in IL-17 producing precursor cells as the mechanism of protection from EAE upon re-injection with myelin antigens as adults. The results could provide a rationale for the presence of autoreactive T cells found in healthy human individuals without autoimmune disease.