1α,25-二羟维生素D_3对患者PBMC分泌的IFN-α和IL-10水平的影响

目 的 探 讨 １α，２５－二羟 维生 素 Ｄ_３（１α，２５－（ＯＨ ）２Ｄ ）对 系 统性 红斑 狼 疮（ＳＬＥ）患 者 外周 血 单个 核 ３细 胞（ＰＢＭ Ｃ）分 泌的 白细 胞 介素 （ＩＬ）－１０ 和 干扰 素 （ＩＦＮ ）－α水平 的 影响 。方法 ２０ 例 ＳＬＥ 患 者和 １０ 名健 康 志愿者 ＰＢＭ Ｃ 的提 取 采 用 Ｆｉｃｏｌ密 度 梯 度 离 心 法 ，ＳＬＥ 组 和 对 照 组 在 不 加 或 加 入 １α，２５－（Ｏ Ｈ ）２Ｄ３ 的 情 况 下 孵 育 ７２ ｈ收 集培 养 上清 ，上 清液 ＩＬ－１０ 和 ＩＦＮ－α水平 检 测采 用酶 联 免疫 吸附 试 验（ＥＬＩＳＡ ）。结 果 与 正常 对 照组 相比 ，ＳＬＥ组 ＰＢＭ Ｃ 中 ＩＬ－１０ 和 ＩＦＮ－α水 平 明 显 增高 （Ｐ＜０．０１）。０．０１ ｍ ｏｌ／Ｌ １α，２５－（Ｏ Ｈ ）２Ｄ３ 的 加 入 明 显 抑 制 了 ＳＬＥ 组ＰＢＭ Ｃ 中 ＩＦＮ －α的 产 生 （Ｐ＜０．０１），增 加 了 ＳＬＥ 组 ＰＢＭ Ｃ 中 ＩＬ－１０ 的 产 生 （Ｐ＜０．０１），但 对 正 常 对 照 组 ＩＦＮ －α和ＩＬ－１０ 水平 无明 显 影响 。结 论 １α，２５－（ＯＨ ）２Ｄ 可 能 抑制 体外 培 养的 ＳＬＥ 患 者 ＰＢＭ Ｃ ＩＦＮ －α的产 生     

长期小剂量阿奇霉素治疗慢性阻塞性肺疾病的初步研究

目的研究长期小剂量阿奇霉素治疗对慢性阻塞性肺疾病(COPD)是否有疗效。方法选择稳定期COPD病人65例,随机分成两组,治疗组口服阿奇霉素0.25g,每日1次,连续用药6周。对照组不用任何药。两组病人在病情加重时,临时应用茁-内酰胺类抗生素。治疗前、治疗6周后检测肺功能1s用力呼气容积(FEV1)和血浆白细胞介素(IL)-6、IL-8及肿瘤坏死因子(TNF)-琢的浓度,并记录临床症状记分。结果60例完成了试验,治疗组30例临床症状改善[治疗前(4.1±0.4)分,治疗后(3.8±0.5)分,P<0.01];FEV1也有改善[治疗前(1.68±0.23)L,治疗后(1.72±0.21)L,P<0.05];血浆IL-8浓度[治疗前(8.5±2.6)pg/ml,治疗后(8.5±2.6)pg/ml]、IL-6浓度[治疗后(7.1±2.8)pg/ml,治疗后(7.0±2.8)pg/ml]及TNF-琢浓度[治疗前(7.6±2.7)pg/ml,治疗后(7.5±2.7)pg/ml]均无明显改变(P>0.05)。对照组(30例)治疗前后各项指标差异无显著性(P>0.05),治疗期间未再见明显副作用。结论长期小剂量阿奇霉素治疗COPD患者可改善临床症状和其肺功能,且安全性好,不影响对血浆IL-8、IL-6及TNF-琢的浓度。     

Immunomodulating Effects of CKBM on the Cytokine Production in Peripheral Blood Mononuclear Cells (PBMCs) from Healthy Volunteers

The current study investigated the immunomodulating effect of CKBM on cytokine induction in peripheral blood mononuclear cells (PBMCs) isolated from 20 healthy volunteers. Cytometric Bead Analysis (CBA) was used to study IL‐2, IL‐4, IL‐6, IL‐10, TNF‐alpha and IFN‐gamma. TNF‐alpha and IL‐6 were significantly increased in a CKBM dose‐ and time‐dependent manner. Flow cytometry analysis showed an increased intracellular staining of IL‐6 but not of TNF‐alpha in CKBM treated PBMCs. In addition, MTT cell cytotoxicity assay showed that CKBM concentrations below 5% did not significantly affect the metabolic activities of PBMCs. The current study indicated that CKBM may modulate the immune response by inducing the secretions of TNF‐alpha and IL‐6, which are cytokine mediators of innate immunity and inflammation preparing or “priming” the body to combat diseases.     

上胸段硬膜外阻滞对脑血管痉挛兔脑组织GR表达及血清炎性细胞因子含量的影响

目的探讨上胸段硬膜外阻滞(HTEB)对蛛网膜下腔出血(SAH)后脑血管痉挛(CVS)兔的基底动脉周围脑组织糖皮质激素受体(GR)mRNA的表达及血清炎性细胞因子含量的影响。方法采用枕大池二次注血法制备兔SAH模型,将45只硬膜外阻滞成功的动物按随机数字表法随机分成3组(n=15):对照组、假手术组和HTEB组;然后各组再分为注血后l、7、14 d三个亚组(n=5)。用经颅多普勒超声检测注射前和注射后1、7、14 d动物基底动脉平均血流速度(Vm)。测量并比较各组基底动脉周围脑组织GR mRNA表达水平及血清炎性细胞因子[肿瘤坏死因子-α(TNF-α)及白细胞介素(IL)-1、6]含量的差异。结果对照组基底动脉Vm、血清中TNF-α、IL-1和IL-6含量最高,HTEB组次之,假手术组最低,三组之间均差异显著(P<0.05)。脑组织中GR表达水平假手术组最高,HTEB组次之,对照组最低,三组之间差异显著(P<0.05)。结论HTEB可增加SAH后CVS的兔基底动脉周围脑组织GR的表达,并抑制TNF-α、IL-1、IL-6过度分泌,从而减轻CVS。     

Influência dos polimorfismos genéticos (IL10/CXCL8/CXCR2/ NFκB) na susceptibilidade das doenças reumatológicas autoimunes

The autoimmune rheumatologic disorders mostly have a common genetic path to the autoimmunity. Several genes have been associated with rheumatologic disorders; therefore, we are analyzing just the ones in those containing several evidences of the existence of association with the risk or protection from autoimmune disorder. The nuclear factor kappa beta (NF‐kappa B), which regulates the autoimmune and anti‐inflammatory responses, is associated with systemic sclerosis (SS), rheumatoid arthritis (RA) and systemic lupus erythematosus (SLE), just as the CXCR2 e CXCL8 genes. On the other hand, the interleukin‐10 (IL‐10), which is an anti‐inflammatory cytokine, is associated with almost all rheumatologic disorders. In this article, we are reviewing the potential roles of these genes in the immune system and in several rheumatologic disorders. In relation to IL‐10, several studies have been carried out, but most of them are controversial – some detected the absence of association, and others found association in different genetic polymorphisms. Conversely, in relation to NF‐kappa B, it was studied just in RA and SLE, and no relevant significant analyses were observed. The genetic polymorphisms of the CXCR2 gene were associated with SS, but not with RA e SLE. On the other side, the genetic polymorphisms of the CXCL8 gene are not associated with SS, but with RA.     

IL-1β、IL-6、TNF-α与注意缺陷多动障碍的相关性

目的:探讨注意缺陷多动障碍(ADHD)儿童体内IL-1β、IL-6、TNF-α含量变化及可能的发病机制;分析IL-1β、IL-6、TNF-α与ADHD症状特征及行为问题的关系。方法:对35例符合DSM-Ⅳ诊断标准的ADHD和25例正常儿童进行血清IL-1β、IL-6、TNF-α浓度测定,选用Achenbach儿童行为量表(CBCL)进行行为评定,比较两组IL-1β、IL-6、TNF-α浓度水平,并与DSM-Ⅳ诊断标准和CBCL得分进行相关分析。结果:ADHD儿童IL-1β较对照组增高,差异有统计学意义(χ2=4.239,P=0.041;Z=2.051,P=0.040);IL-6较对照组增高,但差异不具统计学意义(χ2=3.138,P=0.074;Z=1.892,P=0.058);TNF-α较对照组降低,差异有统计学意义(χ2=5.173,P=0.023;Z=2.792,P=0.005);TNF-α与注意缺陷因子、多动/冲动因子负相关(r=-0.377,P=0.003;r=-0.274,P=0.034);IL-1β与注意缺陷因子正相关(r=0.273,P=0.035);TNF-α与CBCL注意问题、违纪行为、攻击行为、外向性、行为问题总分负相关(r=-0.325,P=0.011;r=-0.396,P=0.002;r=-0.306,P=0.017;r=-0.324,P=0.011;r=-0.346,P=0.007)。结论:ADHD儿童存在高水平的IL-1β和低水平的TNF-α;IL-1β尤其是TNF-α与ADHD注意缺陷症状及某些行为问题间存在关联性。     

Distribution of cytokine gene polymorphisms in six Orang Asli subgroups in Peninsular Malaysia

Cytokines are involved in immune responses and the pathogenesis of various diseases. Allelic variations within the genes coding for various ∼30 kDa cytokine protein/glycoproteins have been reported for many populations and have been the subjects of many ancestry and health analyses. In this study, we typed 22 single nucleotide polymorphisms (SNPs) in 13 cytokine genes of 165 Orang Asli individuals by using sequence specific primer-polymerase chain reaction (SSP-PCR) assay. The volunteers came from all across the Peninsular of Malaysia and belong to six Orang Asli subgroups; Batek, Kensiu, Lanoh, Che Wong, Semai and Orang Kanaq. Here we report our general findings and original genotype data and their associated analyses (Hardy–Weinberg proportions, estimation of allele and haplotype frequencies) can be found in the supplementary files and will be held at Allele Frequency Net Database (AFND).     

Proteomics profiling reveals inflammatory biomarkers of antidepressant treatment response: Findings from the CO-MED trial

Animal and human studies suggest an association between depression and aberrant immune response. Further, common inflammatory markers may change during the course of antidepressant treatment in patients. The objective of this study was to evaluate changes in inflammatory markers and clinical outcomes from subjects enrolled in the Combining Medications to Enhance Depression Outcome (CO-MED) trial. At baseline and week 12 (treatment completion), plasma samples of 102 participants were analyzed via a multiplex assay comprised of inflammatory markers using a 27-plex standard assay panel plus a 4-plex human acute phase xMAP technology based platform. We carried out analyses in two steps. First, t-tests were used to identify inflammatory marker levels that changed between baseline and week 12. For markers that were altered, logistic regression models were then conducted to look for associated changes in remission at week 12. Among the 31 inflammatory markers analyzed, several cytokines (IL-5, IFN-γ, IL-13), two chemokines (Eotaxin-1/CCL11, RANTES) and an acute-phase reactant (serum amyloid P component) showed change from baseline to week 12. However, only two indicated differential remission responses. Interestingly, increased levels of Eotaxin-1/CCL11 correlated with remission at week 12, whereas decreased levels of IFN-γ correlated with non-remission at week 12. Results suggest that these inflammatory proteins may serve as predictors of treatment response.     

Impact of early life exposure to ionizing radiation on influenza vaccine response in an elderly Japanese cohort

The objective of this study was to evaluate effects of whole body radiation exposure early in life on influenza vaccination immune responses much later in life. A total of 292 volunteers recruited from the cohort members of ongoing Adult Health Study (AHS) of Japanese atomic bomb (A-bomb) survivors completed this observational study spanning two influenza seasons (2011–2012 and 2012–2013). Peripheral blood samples were collected prior to and three weeks after vaccination. Serum hemagglutination inhibition (HAI) antibody titers were measured as well as concentrations of 25 cytokines and chemokines in culture supernatant from peripheral blood mononuclear cells, with and without in vitro stimulation with influenza vaccine. We found that influenza vaccination modestly enhanced serum HAI titers in this unique cohort of elderly subjects, with seroprotection ranging from 18 to 48% for specific antigen/season combinations. Twelve percent of subjects were seroprotected against all three vaccine antigens post-vaccination. Males were generally more likely to be seroprotected for one or more antigens post-vaccination, with no differences in vaccine responses based on age at vaccination or radiation exposure in early life. These results show that early life exposure to ionizing radiation does not prevent responses of elderly A-bomb survivors to seasonal influenza vaccine.