银杏叶提取物对树突状细胞和Th1/Th2细胞因子的影响

目的研究银杏叶提取物对不稳定型心绞痛患者(UAP)树突状细胞(DC)功能和Th1/Th2细胞因子的影响。方法将54例UAP分为常规治疗组(对照组,27例)和常规加银杏叶提取物组(银杏叶组,27例),分别于治疗前及治疗后4周取血,分离外周血单个核细胞,在含粒细胞、巨噬细胞、集落刺激因子和白介素4的培养条件下制备DC。用流式细胞仪检测DC表面CD86(B7-2)的表达;混合淋巴细胞反应(MLR)检测DC对同种异体T淋巴细胞的刺激能力;ELISA法测定血液中的细胞因子IFN-γ和IL-4;比浊法测定血C反应蛋白(CRP)。体外实验观察银杏内酯B对DC CD86表达的直接影响。结果与对照组比较,银杏叶提取物可进一步抑制DC功能(P<0.01),同时显著降低血CRP水平(P<0.05)和血IFN-γ浓度(P<0.01);银杏内酯B对DC CD86表达有直接的抑制作用(P<0.01)。结论银杏叶提取物对DC的抑制和由此对患者炎性反应的抑制可能是其治疗心绞痛的机制之一。     

IL-21 Is Associated With Virological Relapse of HBeAg Positive Chronic Hepatitis B After Discontinuance of Entecavir

Background: To investigate the association between interleukin-21 (IL-21) expression level and virological relapse (VR) of HBeAg positive chronic hepatitis B (CHB) after discontinuance of entecavir (ETV).Methods: The serum IL-21 level of 112 CHB patients was measured at 0, 12, 24, 52, and 104 weeks after ETV discontinuance. ELISA was used for the measurement of serum IL-21 level. VR was defined as two continuous examinations with an interval of 1 month with both showing HBV DNA >10 000 copies/mL after drug discontinuance.Results: The serum IL-21 levels at 0, 12, 24, 52, and 104 weeks after discontinuance of ETV were significantly higher in the durable virological remission (DVR) group than in the VR group (all P < .01). The area under the ROC curve (AUC) was 0.728 (95% CI: 0.630-0.827, P < .001), while the best cut-off value was 49.8 pg/mL. Multivariate Cox model showed that the factors affecting the relapse included age, followed by HBsAg level at the serological conversion of HBeAg and serum IL-21 level (all P < .05).Conclusion: Serum IL-21 level at ETV discontinuance is an independent risk factor for CHB relapse. IL-21 acts as an immunomodulatory factor in maintaining DVR in HBeAg positive CHB patients after ETV discontinuance.     

Gestational poly(I:C) attenuates,not exacerbates,the behavioral,cytokine and mTOR changes caused by isolation rearing in a rat ‘dual-hit’ model for neurodevelopmental disorders

Many psychiatric illnesses have a multifactorial etiology involving genetic and environmental risk factors that trigger persistent neurodevelopmental impairments. Several risk factors have been individually replicated in rodents, to understand disease mechanisms and evaluate novel treatments, particularly for poorly-managed negative and cognitive symptoms. However, the complex interplay between various factors remains unclear. Rodent dual-hit neurodevelopmental models offer vital opportunities to examine this and explore new strategies for early therapeutic intervention. This study combined gestational administration of polyinosinic:polycytidylic acid (poly(I:C); PIC, to mimic viral infection during pregnancy) with post-weaning isolation of resulting offspring (to mirror adolescent social adversity). After in vitro and in vivo studies required for laboratory-specific PIC characterization and optimization, we administered 10 mg/kg i.p. PIC potassium salt to time-mated Lister hooded dams on gestational day 15. This induced transient hypothermia, sickness behavior and weight loss in the dams, and led to locomotor hyperactivity, elevated striatal cytokine levels, and increased frontal cortical JNK phosphorylation in the offspring at adulthood. Remarkably, instead of exacerbating the well-characterized isolation syndrome, gestational PIC exposure actually protected against a spectrum of isolation-induced behavioral and brain regional changes. Thus isolation reared rats exhibited locomotor hyperactivity, impaired associative memory and reversal learning, elevated hippocampal and frontal cortical cytokine levels, and increased mammalian target of rapamycin (mTOR) activation in the frontal cortex – which were not evident in isolates previously exposed to gestational PIC. Brains from adolescent littermates suggest little contribution of cytokines, mTOR or JNK to early development of the isolation syndrome, or resilience conferred by PIC. But notably hippocampal oxytocin, which can protect against stress, was higher in adolescent PIC-exposed isolates so might contribute to a more favorable outcome. These findings have implications for identifying individuals at risk for disorders like schizophrenia who may benefit from early therapeutic intervention, and justify preclinical assessment of whether adolescent oxytocin manipulations can modulate disease onset or progression.     

Cytokine-mediated inflammation, tumorigenesis, and disease-associated JAK/STAT/SOCS signaling circuits in the CNS

Cytokines are plurifunctional mediators of cellular communication. The CNS biology of this family of molecules has been explored by transgenic approaches that targeted the expression of individual cytokine genes to specific cells in the CNS of mice. Such transgenic animals exhibit wide-ranging structural and functional alterations that are linked to the development of distinct neuroinflammatory responses and gene expression profiles specific for each cytokine. The unique actions of individual cytokines result from the activation of specific receptor-coupled cellular signal transduction pathways such as the JAK/STAT tyrosine kinase signaling cascade. The cerebral expression of various STATs, their activation, as well as that of the major physiological inhibitors of this pathway, SOCS1 and SOCS3, is highly regulated in a stimulus- and cell-specific fashion. The role of the key IFN signaling molecules STAT1 or STAT2 was studied in transgenic mice (termed GIFN) with astrocyte-production of IFN-α that were null or haploinsufficient for these STAT genes. Surprisingly, these animals developed either more severe and accelerated neurodegeneration with calcification and inflammation (GIFN/STAT1 deficient) or severe immunoinflammation and medulloblastoma (GIFN/STAT2 deficient). STAT dysregulation may result in a signal switch phenomenon in which one cytokine acquires the apparent function of an entirely different cytokine. Therefore, for cytokines such as the IFNs, the receptor-coupled signaling process is complex, involving the coexistence of multiple JAK/STAT as well as alternative pathways. The cellular compartmentalization and balance in the activity of these pathways ultimately determines the repertoire and nature of CNS cytokine actions.     

Detection of interleukin-1 and interleukin-6 in adult rat brain, following mechanical injury, by in vivo microdialysis: evidence of a role for microglia in cytokine production

In vivo levels of interleukin-1 (IL-1) and IL-6, present in the interstitial spaces of brain, have been repeatedly monitored up to 7 days after insertion of a microdialysis probe, designed to induce mechanical trauma to the brain. IL-1 is barely detectable immediately after implantation but over a 24-48 h period a 15-fold increase is seen. In contrast IL-6 levels at day 0 are high, increasing slightly (10%) by day 1 but decreasing to 40% by day 2. The temporal pattern of IL-6 recovery in the cerebrospinal fluid was similar to that in the dialysate but the levels were significantly lower and may reflect diffusion from the site of the probe lesion. Cellular sources of these cytokines include macrophages and neutrophils, which have infiltrated the lesion and microglia resident in the brain, which can be identified at the lesion site within 24 h of probe implantation. The astrocytic response to injury, evidenced by increased glial fibrillary acidic protein staining occurs much later, by day 7, and is unlikely to be responsible for IL-1 and IL-6 production found at 24-48 h. Since upon isolation and stimulation of microglia in vitro with lipopolysaccharide IL-1 and IL-6 can be measured in the supernatant, it would appear that they have the capacity to produce cytokines in vivo. Localised synthesis of cytokines at sites of brain injury by microglia would further stimulate microglia in an autocrine manner and also propagate the astrocytic reaction.     

负性生活事件对抑郁症患者血清细胞因子水平的影响

目的　探讨负性生活事件对抑郁症患者血清细胞因子水平的影响。方法　采用酶联免疫吸附法 (EL SIA)对有负性生活事件诱因的抑郁症患者 2 3例、无诱因的抑郁症患者 2 9例和 2 9名正常人的血清白介素 2 (IL 2 )、可溶性白介素 2受体 (sIL 2R)、白介素 10 (IL 10 )和白介素 12 (IL 12 )水平进行检测。结果　 3组间IL 2、sIL 2R及IL 12水平存在显著性差异 ,而IL 10则 3组间无显著性差异 ,有负性生活事件诱因组IL 2及sIL 2R水平明显低于无诱因组和对照组 (P <0 0 1) ;有诱因组其负性生活事件对患者心理活动影响的严重程度与IL 2和sIL 2R水平呈负相关(P <0 0 5 )。结论　负性生活事件对抑郁症患者的细胞免疫激活系统有抑制作用 ,IL 2可能是起主要的中介作用。     

Serum IL-21 levels are elevated in atopic dermatitis patients with acute skin lesions

Background

Interleukin (IL)-21 is a member of the type I cytokine family and plays a role in the pathogenesis of T helper type 2 allergic diseases. It has been reported that IL-21 expression is upregulated in acute skin lesions in atopic dermatitis (AD) patients; however, little is known about the serum IL-21 levels of AD patients. The aim of this study was to quantify the serum IL-21 levels of AD patients and to evaluate the relationships between the serum IL-21 level and disease severity, laboratory markers, and eruption type in AD patients.

腹腔镜以及开腹子宫肌瘤切除术后CRP、TNF-α、IL-6水平变化分析

目的 探讨腹腔镜和开腹子宫肌瘤切除手术对机体CRP、TNF-α、IL-6的影响.方法 选取我院收治的110例子宫肌瘤并行手术治疗患者,根据其不同的手术方式将其分为腹腔镜组以及开腹手术组,每组55例,比较两组患者的手术时间、出血量、排气时间、并发症情况及术前术后的CRP、TNF-α、IL-6水平变化情况.结果 腹腔镜组患者的手术时间明显长于开腹手术组,但术中出血少、术后排气快,组间比较差异有统计学意义(P＜0.05),术前两组患者的血清CRP、TNF-α、IL-6水平比较差异无统计学意义(P＞0.05),且两组术前TNF-α均明显高于正常值,术后90min两组CRP、TNF-α、IL-6水平均达到最高峰,腹腔镜手术后CRP、TNF-α、IL-6指标于术后第3d恢复正常,而开腹手术组患者术后第7d才恢复至正常水平,且手术开始后90min、术后第1、3d两组患者CRP、TNF-α、IL-6指标比较差异具有统计学意义(P＜0.05).结论 与开腹手术相比,腹腔镜子宫肌瘤切除术所带来的创伤更小、有利于患者的术后康复,有效减少术后并发症,而其可能与腹腔镜手术所导致的机体抗炎因子分泌减少有关.     

溃疡性结肠炎相关的分子生物学研究进展

溃疡性结肠炎(ulcerative colitis,UC)是一种以腹痛、腹泻及黏液脓血便为典型临床表现的慢性肠道疾病,其病灶呈连续性弥漫性分布,主要累及结肠的黏膜及黏膜下层.据流行病学统计,UC的发病率呈逐步增高的趋势,而其病因及发病机制尚未完全明确,目前认为是多元化因素综合作用的结果.本文就与UC相关的基因、细胞因子以及相关受体的研究进展作一综述.     

细胞因子IL-1、IL-6和IL-8水平与胃窦癌恶病质关系

目的探讨胃窦癌病人血清细胞因子白细胞介素（IL）-1、IL-6和IL-8的水平与恶病质发生的关系。方法125例胃窦癌病人分为恶病质组与非恶病质组,将近6个月体质量下降〉10％者定义为恶病质病人。通过放射免疫学方法对胃窦癌病人及健康对照组进行血清IL-1、IL-6和IL-8含量的检测。结果胃窦癌病人血清中3种细胞因子含量较对照组均显著升高（Z=-8．186～-4．665,P〈0．05）,胃窦癌恶病质病人血清IL-6和IL-8含量较非恶病质病人显著升高（Z=-5．018、-3．134,P〈0．05）。多因素Logistic回归分析显示,IL-6（OR=1．048,95％CI：1．021～1．075）和IL-8（OR=3．150,95％CI：0．988～10．037）为恶病质发生的高风险性因素。结论血清IL-6和IL-8水平与胃窦癌病人恶病质的发生具有相关性。