脓毒症患儿血浆miR-146a、miR-223表达与IL-6、IL-10、TNF-α 水平变化的临床意义分析

目的:探讨脓毒症患儿血浆微RNA-146a(miR-146a)、miR-223表达及与白细胞介素-6(IL-6)、IL-10和肿瘤坏死因子(TNF-α)的关系。方法:选取2016年2月至2017年2月在我院治疗的脓毒症患儿44例作为脓毒症组,同时选取32例全身性炎症反应综合征(SIRS)患儿(SIRS组)和40例健康儿童(对照组),检测和比较各组患儿血浆miR-146a、miR-223、IL-6、IL-10和TNF-α的表达,同时采用序贯器官衰竭估计评分(SOFA评分)评价脓毒症患儿的病情。结果:脓毒症组miR-146a、miR-223、IL-6和IL-10表达分别为(5.90±1.22)×10~(-5)、(13.17±2.13)×10~(-4),20.21(12.06,64.13)ng/L和17.60(8.94,70.11)pg/m L,明显高于SIRS组和对照组(P0.05);脓毒症组和SIRS组血浆TNF-水平分别为(22.50(22.50,29.80)pg/m L和(23.40(19.41,30.01)pg/m L,明显高于对照组(P0.05);患儿miR-146a、miR-223与SOFA评分呈正相关(rs=0.411和0.321,P0.05),而血浆IL-6、IL-10及TNF-α水平与SOFA评分无显著相关性(P0.05);miR-146a与血浆IL-6、IL-10水平呈显著正相关(rs=0.297和0.301,P0.05),miR-223与血浆TNF-α水平呈正相关(rs=0.284,P0.05)。结论:脓毒症患儿血浆miR-146a和miR-223表达、IL-6、IL-10和TNF-α水平均异常上调,且血浆miR-146a和miR-223表达与IL-6、IL-10、TNF-水平及病情程度显著相关。     

脓毒症患者血清FGF-21、MR-proADM、炎性因子与预后的关系分析

目的:探讨血清人成纤维细胞生长因子-21(FGF-21)、肾上腺髓质素前体中段肽(MR-proADM)、炎性因子与脓毒症患者预后的关系。方法:选取2015年9月至2018年9月我院收治的脓毒症患者160例(脓毒症组),按病情严重程度分为轻度脓毒症组(A组)56例、严重脓毒症组(B组)53例,脓毒性休克组(C组)51例,另选取同期50例健康体检者作为健康对照组。检测各组血清FGF-21、MR-proADM和炎性因子[(白细胞(WBC),白细胞介素-6(IL-6),肿瘤坏死因子-α(TNF-α),白细胞介素-10(IL-10)]水平,记录脓毒症患者序贯性器官功能衰竭评分(SOFA)和急性生理学与慢性健康状况评分系统Ⅱ(APACHEⅡ)评分及28 d预后。采用受试者工作特征(ROC)曲线分析FGF-21、MR-proADM、炎性因子单独及联合评估脓毒症预后的价值。采用Spearman相关分析FGF-21、MR-proADM和炎性因子与APACHEⅡ评分、SOFA评分的相关性。结果:脓毒症组血清FGF-21、MR-proADM和炎性因子WBC、IL-6、TNF-α、IL-10水平均明显高于健康对照组(均P0.05),且随着脓毒症病情的加重,患者血清FGF-21、MR-proADM和炎性因子水平逐渐升高。脓毒症患者中28d死亡43例(26.88%),其中A组8例(14.29%)、B组12例(22.64%)、C组23例(45.10%)。ROC曲线分析显示,联合检测评估脓毒症患者病死率的曲线下面积(AUC)、敏感度及特异度均高于单一检测。脓毒症患者血清FGF-21、MR-proADM、WBC、IL-6、TNF-α与APACHEⅡ评分及SOFA评分均呈正相关性(P0.05),此外,IL-10与SOFA评分呈正相关性(P0.05),与APACHEⅡ评分无相关性(P0.05)。结论:脓毒症患者血清FGF-21、MR-proADM水平升高,检测FGF-21、MR-proADM和炎性因子有助于评估脓毒症患者的病情及预后。     

抑郁症患者血清miR-135a、miR-221表达水平与认知功能、事件相关电位P300和炎症细胞因子的相关性分析

目的:探讨抑郁症患者血清微小核糖核酸(mi R)-135a、mi R-221表达水平与认知功能、事件相关电位P300和炎症细胞因子的相关性。方法:选择2019年1月至2021年1月我院收治的216例抑郁症患者(抑郁症组)和同期于我院体检的200例健康志愿者(对照组)。检测血清mi R-135a、mi R-221表达水平及白细胞介素-6(IL-6)、超敏C反应蛋白(hs-CRP)、肿瘤坏死因子-α(TNF-α)水平。采用蒙特利尔认知评估量表(MoCA)、简易精神状态检查量表(MMSE)评估认知功能。采用全功能肌电诱发电位仪检测P3潜伏期和P3波幅。Pearson相关性分析mi R-135a、mi R-221表达水平与MoCA评分、MMSE评分、IL-6,hs-CRP,TNF-α、P3潜伏期和P3波幅的相关性。结果:抑郁症组血清mi R-221表达水平、P3潜伏期,血清IL-6、hs-CRP、TNF-α水平高于对照组(P<0.05),mi R-135a表达水平、MMSE评分、MoCA评分、P3波幅低于对照组(P<0.05)。mi R-221表达水平与P3潜伏期,血清IL-6、hs-CRP、TNF-α水平呈正相关(P<0.05),与MMSE评分、MoCA评分、P3波幅呈负相关(P<0.05);mi R-135a表达水平与P3潜伏期,血清IL-6、hs-CRP、TNF-α水平呈负相关(P<0.05),与MMSE评分、MoCA评分、P3波幅呈正相关(P<0.05)。结论:抑郁症患者血清mi R-135a表达水平降低,mi R-221表达水平增高,mi R-135a低表达和mi R-221高表达与抑郁症患者认知功能降低、机体炎症反应有关。     

调节性T 细胞在发热结缔组织病患者外周血中的表达及临床意义

目的:研究Treg细胞在发热CTD患者外周血表达对结核感染的诊断价值。方法:对103例发热CTD患者进行T-SPOT.TB试验,将39例阳性者设为实验组-1,进行抗结核治疗,将64例阳性者设为实验组-2,另选取40例健康者作为对照组,检测三组外周血CD4+CD25+Treg细胞、Foxp3基因、IL-10、TGF-β的表达。结果:实验组CD4+CD25+Foxp3 Treg细胞占CD4+T比例高于对照组(P0.05),实验组-1治疗前外周血CD4+CD25+Foxp3 Treg细胞占CD4+T比例高于实验组-1治疗后、实验组-2(P0.05);实验组TGF-β表达量低于对照组(P0.05),实验组-1治疗前低于实验组-1治疗后及实验组-2(P0.05);实验组-1治疗前IL-10表达量低于实验组-1治疗后、实验组-2及对照组(P0.05)。结论:CD4+CD25+Foxp3 Treg细胞在发热CTD伴有结核感染患者外周血中的表达升高,其变化可作为结核感染诊断的辅助性指标。     

双氢杨梅素对缺氧诱导的心肌细胞炎症反应和凋亡的影响及机制

目的:探讨双氢杨梅素对缺氧诱导的心肌细胞炎症和凋亡的影响及其可能调控机制。方法:将心肌细胞(H9C2细胞系)缺氧处理建立细胞模型,随机分为4组:对照组、对照+双氢杨梅素组、缺氧组、缺氧+双氢杨梅素组。对照+双氢杨梅素组和缺氧+双氢杨梅素组分别加入5μmol/L的双氢杨梅素孵育24 h,对照组和缺氧组分别加入同等体积的DMSO孵育24 h。实时PCR检测心肌细胞CD40、IL-1β、IL-6、TNF-α、mi RNA-145-5p的m RNA水平;ELISA检测IL-1β、IL-6和TNF-α的浓度;MTT实验检测心肌细胞生存率;Tunel法检测心肌细胞凋亡;Western blot检测心肌细胞Cleaved Caspase3的表达。结果:与对照组和对照+双氢杨梅素组相比,缺氧组CD40、IL-1β、IL-6、TNF-α的m RNA水平升高(P0.05),IL-1β、IL-6、TNF-α浓度显著升高(P0.05),mi RNA-145-5p的m RNA水平显著降低(P0.05),心肌细胞生存率显著降低(P0.05),心肌细胞凋亡显著增加(P0.05),Cleaved Caspase3的蛋白表达显著增加;与缺氧组相比,缺氧+双氢杨梅素组CD40、IL-1β、IL-6、TNF-α的m RNA水平显著降低(P0.05),IL-1β、IL-6、TNF-α浓度显著降低(P0.05),mi RNA-145-5p的m RNA水平显著增加(P0.05),心肌细胞生存率显著增加(P0.05),心肌细胞凋亡显著降低(P0.05),Cleaved Caspase3的蛋白表达显著降低。结论:双氢杨梅素可抑制缺氧诱导的心肌细胞炎症和凋亡,其机制可能与双氢杨梅素上调mi RNA-145-5p进一步抑制CD40介导的炎症反应和凋亡有关。     

氟康唑胶囊联合知柏地黄丸治疗滴虫性阴道炎的疗效及对患者血清IL-10和TNF-α水平的影响

目的:探讨氟康唑胶囊联合知柏地黄丸对滴虫性阴道炎患者血清白细胞介素-10(IL-10)、肿瘤坏死因子-α(TNF-α)的影响及临床疗效。方法:收集我院就诊的78例滴虫性阴道炎患者,随机分为实验组和对照组,各39例。对照组患者给予氟康唑胶囊治疗,实验组在对照组基础上给予知柏地黄丸治疗。观察并比较两组患者治疗前后IL-10、TNF-α、阴道健康评分及临床疗效。结果:与治疗前相比,两组患者治疗后血清IL-10、TNF-α水平均显著下降,阴道健康评分均明显升高,差异具均有统计学意义(P0.05);与对照组相比,实验组患者治疗后血清IL-10、TNF-α水平较低,阴道健康评分和临床治疗总有效率均较高,差异均具有统计学意义(P0.05)。结论:氟康唑胶囊联合知柏地黄丸能够有效提高滴虫性阴道炎患者的临床疗效,可能与其显著降低血清IL-10、TNF-α水平有关。     

原发性舍格伦综合征患者血清炎症因子、外周血淋巴细胞亚群分布与病情严重程度的相关性探究

目的:探讨原发性舍格伦综合征(pSS)患者血清炎症因子、外周血淋巴细胞亚群分布与病情严重程度的相关性。方法:选取2016年1月至2018年8月我院收治的105例pSS患者为研究对象,根据病程将全部患者分为初发组(n=51)、复发组(n=22)与稳定组(n=32),并选取同期来我院体检的50例健康成人作为对照组。比较各组患者的血清肿瘤坏死因子-α(TNF-α)、白细胞介素-1β(IL-1β)与白细胞介素-32(IL-32)水平以及外周血淋巴细胞亚群分布。采用Pearson相关分析探讨pSS患者欧洲抗风湿联盟干燥综合征疾病活动指数(ESSDAI)与其血清炎症因子、外周血淋巴细胞亚群分布的相关性。结果:⑴血清TNF-α、IL-1β水平:初发组、复发组稳定组对照组;血清IL-32水平:初发组、复发组对照组,复发组稳定组。⑵外周血CD4~+/CD8~+比值:初发组、复发组、稳定组对照组;外周血Th1/Th2比值:初发组、复发组对照组;外周血Th17/Treg比值:初发组、复发组、稳定组对照组,且复发组稳定组。四组研究对象的外周血T淋巴细胞、B淋巴细胞、NK细胞的百分比比较差异均无统计学意义(P0.05)。⑶Pearson相关分析显示pSS患者的ESSDAI评分与血清TNF-α、IL-1β、IL-32水平及外周血Th17/Treg比值均呈显著正相关(r=0.271、0.306、0.251、0.198,P0.05)。结论:pSS患者的血清TNF-α、IL-1β与IL-32水平及外周血CD4~+/CD8~+、Th1/Th2、Th17/Treg比值均明显升高,其中血清TNF-α、IL-1β、IL-32水平、外周血Th17/Treg比值与疾病活动度呈明显正相关。     

强直性脊柱炎患者外周血TNF-α、IL-17、IL-33的表达及与疾病活动程度的相关性研究

目的:探讨强直性脊柱炎(AS)患者外周血肿瘤坏死因子-α(TNF-α)、白细胞介素-17(IL-17)、白细胞介素-33(IL-33)的表达及与疾病活动程度的相关性。方法:选取2016年5月到2017年6月在我院接受治疗的AS患者74例作为研究组,另选取同期在我院体检的健康志愿者40例作为对照组,根据AS病情活动评分量表(BASDAI)将研究组患者分为A组(BASDAI4分,32例)和B组(BASDAI得分≦4分,42例),比较研究组和对照组外周血中TNF-α、IL-17、IL-33水平,比较A组和B组外周血中TNF-α、IL-17、IL-33、C反应蛋白(CRP)、红细胞沉降率(ESR),采用Spearman相关性分析TNF-α、IL-17、IL-33水平与BASDAI得分及CRP、ESR的相关性。结果:研究组外周血中TNF-α、IL-17、IL-33水平明显高于对照组,差异有统计学意义(P0.05),A组外周血中TNF-α、IL-17、IL-33、CRP、ESR明显高于B组,差异有统计学意义(P0.05);AS患者TNF-α、IL-17、IL-33水平与BASDAI得分及CRP、ESR水平均呈正相关(P0.05)。结论:TNF-α、IL-17、IL-33在AS患者外周血中呈现高表达,并且与患者BASDAI得分及CRP、ESR水平呈正相关。     

人肿瘤坏死因子α特异性结合miR-146b的新生物学特性研究

目的:探讨人肿瘤坏死因子α(TNF-α)作为micro RNA(mi RNA)结合蛋白的生物学特性。方法:Western印迹检测LPS激活的U937细胞中TNF-α蛋白表达水平,RT-PCR检测几种炎症相关的mi RNA在激活前后表达水平的变化;用RNA结合蛋白免疫共沉淀(RIP)技术钓取U937细胞中TNF-α结合的mi RNA,RT-PCR检测RIP产物中上述几种mi RNA的含量;用凝胶阻滞实验检测TNF-α与mi RNA是否直接结合。结果:LPS激活的U937细胞中能检测到膜结合型和可溶性2种形式的TNF-α,细胞激活前后mi R-16和mi R-21的表达水平在检测的几种mi RNA中最高,mi R-146b和mi R155次之;而RIP产物中mi R-146b的水平在实验组和对照组中有显著差异,其他mi RNA差异不明显;凝胶阻滞实验结果显示mi R-146b能与人TNF-α直接结合。结论:首次证实人TNF-α能够直接特异地结合mi R-146b,提示TNF-α可能作为mi RNA结合蛋白发挥生物学功能。     

细胞因子(IL-6、IL-10、TNF-α)在华支睾吸虫病肝功能损伤中作用的研究

目的探讨华支睾吸虫病患者白细胞介素-6(IL-6)、白细胞介素-10(IL-10)、肿瘤坏死因子-α(TNF-α)水平与肝功能的临床关系。方法试验组为50例未经治疗的华支睾吸虫病患者,并参照ChildPugh肝功能分级法,按照评分将其分成Ⅰ、Ⅱ、Ⅲ三组;对照组为20例健康献血员。采集试验组及对照组静脉血,用全自动生化分析仪检测血浆中总胆红素(TBIL)、血清白蛋白(ALB)和谷丙转氨酶(ALT)含量;采用放射免疫法检测血清IL-6、IL-10及TNF-α含量,并进行统计分析。结果华支睾吸虫病患者血清IL-6、IL-10、TNF-α水平明显高于健康人对照组(P0.01)。随着患者肝功能受累程度的加重,血清IL-6、IL-10及TNF-α含量依次递增,Ⅰ组和Ⅲ组间差异均有统计学意义(P0.01)。IL-6、TNF-α含量与其TBIL(γ=0.470、P0.01,γ=0.518、P0.01)及ALT(γ=0.497、P0.01,γ=0.285、P0.05)呈正相关,与ALB呈负相关(γ=-0.620、P0.01,γ=-0.665、P0.01)。结论华支睾吸虫病患者IL-6和TNF-α表达增强,共同参与介导了华支睾吸虫病肝损伤过程。     

Neutrophil CD64 expression and serum IL-8: sensitive early markers of severity and outcome in sepsis

The aim of the present study was to investigate which biomarker/s reliably assess severity and mortality early in the sepsis process. In 47 critically-ill patients within the 24h of septic onset, Interleukins (IL)-8, -1beta, -6, -10, and -12p70, tumor necrosis factor-alpha (TNF-alpha), procalcitonin (PCT) and C-reactive protein (CRP) were measured in serum. Additionally, CD64 expression was measured in neutrophils. In early sepsis, neutrophil CD64 expression and IL-8 levels are the only biomarkers that increased with sepsis severity, differentiating disease stages: sepsis, severe sepsis and septic shock (p<0.001). The biomarkers that best evaluate the severity of sepsis (via APACHE II) were CD64, IL-8 and IL-6 (p<0.01), and the severity of organ failure (via SOFA) were CD64 and IL-8 (p<0.01). CD64 expression and IL-8 levels were associated with mortality within 28-days (OR=1.3, p=0.01 for CD64 and OR=1.26, p=0.024 for IL-8 by logistic regression analysis) and ROC curve analysis showed high sensitivity and specificity for predicting sepsis stages and the 28 day mortality. We conclude that there is an early increase of neutrophil CD64 expression and IL-8 levels during sepsis. Based on this single measurement it is possible to reliably assess the stage, detect the severity and predict the 28-day mortality of sepsis.     

脓毒症患者血清炎症因子与SOFA评分的关系研究

目的:探究脓毒症患者血清炎症因子与序贯器官衰竭评估(SOFA)评分的关系,从而有助于评价患者病情严重程度,科学判断预后效果。方法:选择2014年1月至2015年12月期间在本院内接受治疗的脓毒血症患者142例作为研究对象。入院后24 h内患者进行血清炎症因子IL-6、PCT、CRP水平测定,同时进行SOFA评分。按照患者在入院治疗28天内生存结局状况进行分组,分别为死亡组(87例)和存活组(55例),另按照患者合并多器官功能障碍综合症(MODS)与否,分为MODS组(76例)和非MODS组(66例),对比不同组别间IL-6、PCT、CRP及SOFA评分差别;对比不同SOFA评分患者血清IL-6、PCT、CRP水平差异,分析其相关性。结果:IL-6、PCT以及SOFA评分比较,死亡组高于存活组,MODS组高于非MODS组,差异有统计学意义(P0.05);SOFA评分越高,血清IL-6、PCT水平越高,差异有统计学意义(P0.05);SOFA评分升高,患者病死率显著增加,SOFA10分,病死率为78.3%,差异有统计学意义(P0.05);Spearman相关分析结果显示,SOFA评分与血清IL-6水平呈显著正相关关系(r=0.261,P=0.012),与血清PCT水平呈正相关关系(r=0.453,P=0.000),SOFA与CRP水平无相关性(r=0.112,P=0.323)。结论:血清IL-6、PCT水平与SOFA评分具有相关性,可以在脓毒症患者病情严重程度及预后状况判断中作为生物学指标进行常规监测。     

IL-23/IL-17轴在脓毒症中的表达及意义

目的:探讨IL-23/IL-17轴在脓毒症患者中的表达及意义.方法:符合诊断标准的脓毒症患者40例,以28天预后为终点,将患者分为存活组(n=21)和病死组(n=19),分析各组病人的急性生理和慢性健康评分(APACHE)Ⅱ和序贯器官衰竭估计(SOFA)评分,同时在入ICU第1天采取外周静脉血做IL-23和IL-17检测,并对病死率和IL-23、IL-17、APACHEⅡ、SOFA做相关性分析.结果:与存活组比较,病死组患者拥有较高的APACHEⅡ和SOFA评分(P<0.01),且外周血的IL-23和IL-17蛋白含量均明显升高(P<0.05).APACHEⅡ和SOFA评分、IL-17和IL-23含量与28天预后有明显的相关性(P<0.05).结论:脓毒症Th17细胞分泌的IL-23/IL-17增加,加重患者病情,在脓毒症发病机制中可能扮演重要角色.     

Sequential measurement of IL-6 blood levels in patients with systemic inflammatory response syndrome (SIRS)/sepsis

This study was undertaken to investigate whether sequential measurement of blood interleukin (IL)-6 levels using chemiluminescent enzyme immunoassay (CLEIA) would be useful for the management of patients with systemic inflammatory response syndrome (SIRS)/sepsis. Forty consecutive patients with SIRS/sepsis admitted to ICU were involved in the study. Blood IL-6 level was measured everyday throughout their ICU stay at the clinical laboratory by CLEIA method. The platelet count and the sequential organ failure assessment (SOFA) score were measured consecutively. The blood IL-6 levels were elevated in SIRS/sepsis patients and were extremely high in patients with septic shock. There was no significant difference in the blood IL-6 level on admission between survivors (n=27) and non-survivors (n=13). However, the mean blood IL-6 level during ICU stay was significantly higher in the non-survivors (p<0.05). There were significant correlation between the peak IL-6 blood level and the lowest platelet count, and between the peak IL-6 blood level and the maximum SOFA score, respectively. The platelet count became lowest 2.0+/-2.0 days later on average, and the SOFA score became maximal 2.5+/-1.4 days later on average following the day when IL-6 reached its peak value. Sequential measurement of blood IL-6 levels by CLEIA is useful in evaluating the severity and in predicting the outcome of the patients with SIRS/sepsis.     

Reduced frequency of circulating regulatory T cells and their related immunosuppressive mediators in treated celiac patients

Background

Regulatory T cells (Tregs) have an important role in the control of the immune responses. This study aimed to compare the frequency of peripheral blood (PB) CD4+?CD25+?FoxP3+?Treg cells and PB and duodenal expression levels of pro- and anti-inflammatory mediators in treated celiac disease (CD) patients and healthy controls.

Methods and results

Duodenal biopsy specimens and PB samples were collected from 60 treated CD patients and 60 controls. Flow cytometry analysis was conducted on peripheral blood mononuclear cell (PBMC) specimens and relative PB and duodenal mRNA expression levels of CD25, forkhead box P3 (Foxp3), interleukin (IL)-10 and granzyme B (GrzB) were evaluated using quantitative real-time PCR. The levels of serum IL-10 and IL-6 were tested with sandwich enzyme-linked immunosorbent assay kits. p values?<?0.05 were considered significant. Flow cytometry analysis showed a significant decrease in the number of Tregs in CD patients’ PBMC specimens (p?=?0.012). CD25 and Foxp3 PB mRNA expressions were also lower in CD patients without reaching the significance level (p?>?0.05). IL-10 PB mRNA and protein expression did not differ between the groups (p?>?0.05), and GrzB PB expression was significantly reduced in CD patients (p?=?0.001). In duodenal specimens of CD patients, while significantly increased CD25, Foxp3 mRNA expression (p?=?0.01 and 0.001, respectively) and decreased IL-10 mRNA expression (p?=?0.02) were observed, GrzB mRNA expression did not differ between groups (p?>?0.05). Moreover, a high serum level of IL-6 was observed in CD patients (p?=?0.001).

Conclusions

Despite following the gluten free diet, there may still be residual inflammation in the intestine of CD patients. Accordingly, finding a therapeutic approach based on strengthening the function of Treg cells in CD might be helpful.

     

血清TRAF-6、MCP-1、sTREM-1、IL-33水平与脓毒症严重程度及与合并急性肾损伤关系的临床分析

目的:探讨脓毒症患者血清肿瘤坏死因子受体相关因子(Tumor necrosis factor receptor-related factor,TRAF)-6、单核细胞趋化蛋白(Monocyte chemotactic protein,MCP)-1、可溶性髓样细胞触发受体(Soluble myeloid cell trigger receptor,s TREM)-1、白介素(Interleukin,IL)-33水平的变化及与病情严重程度及合并急性肾损伤(acute kidney injury, AKI)的相关性。方法:选择2014年2月到2018年7月在我医院ICU病房进行诊治的脓毒症患者145例,分析脓毒症相关性急性肾损伤(sepsis-associated AKI,SAKI)的发生情况,比较SAKI和非SAKI患者血清TRAF-6、MCP-1、s TREM-1、IL-33水平,采用Pearson相关分析血清TRAF-6、MCP-1、s TREM-1、IL-33含量与APACHEⅡ评分、SOFA评分的相关性,多因素logistic回归分析脓毒症患者发生SAKI的影响因素。结果:在145例患者中,发生SAKI者69例,发生率为47.6%。SAKI组患者的年龄、性别、原发病、白细胞(white blood cell,WBC)计数、C反应蛋白(C reactive protein,CRP)、降钙素原(procalcitonin,PCT)、体重指数、BUN、Scr与eGFR值与非SAKI组患者对比差异均无统计学意义(P0.05)。SAKI组患者APACHEⅡ评分、SOFA评分血清TRAF-6、MCP-1、s TREM-1、IL-33含水平含量均显著高于非SAKI组患者(P0.05)。Pearson相关性分析显示血清TRAF-6、MCP-1、s TREM-1、IL-33水平与SAKI患者的急性生理和慢性健康Ⅱ(acute physiology and chronic health evaluation II,APACHEⅡ)评分、序贯多器官功能障碍(sequential organ failure assessment,SOFA)评分均呈显著正相关性(P0.05)。logistic回归分析显示血清TRAF-6、MCP-1、s TREM-1、IL-33水平升高均为影响SAKI发生的独立危险因素(P0.05)。结论:血清TRAF-6、MCP-1、s TREM-1、IL-33水平与脓毒症严重程度显著相关,可能作为诊断和治疗SAKI的参考指标及干预靶点。     

Keratinocyte growth factor induces expansion of murine peripheral CD4+Foxp3+ regulatory T cells and increases their thymic output

Keratinocyte growth factor (KGF) has been shown to reduce the incidence and severity of graft-versus-host disease by prevention of epithelial damage and by modulating alloreactivity. Since regulatory T cells (Treg) play a crucial role in immune modulation, we evaluated the effects of exogenous KGF on peripheral CD4(+)Foxp3(+) Treg and the generation of Treg in the thymus of normal mice. A 3-day course of KGF induced a rapid selective increase in the number of highly suppressive CD4(+)Foxp3(+) Treg. Blood Treg numbers remained elevated for >2 mo, but the frequency normalized after 2 wk due to a concomitant increase in CD4(+)Foxp3(-) T cells. Analysis of single joint TCR excision circles frequency and Ki-67 expression in peripheral blood Treg showed that the early selective increase of Treg was predominantly accounted for by peripheral expansion. Thymectomy before KGF administration did not affect the early selective increase of Treg but abrogated the late increase in CD4(+) T cell numbers, thereby showing its dependence on thymic output. Collectively, these results show that KGF induces an increase in blood CD4(+)Foxp3(+) Treg numbers via two independent mechanisms. First by selective peripheral expansion of Treg and thereafter by enhanced thymic output of newly developed Treg.     

Immunomodulatory effects of glycine on LPS-treated monocytes: reduced TNF-alpha production and accelerated IL-10 expression.

Cytokines play a pivotal role in the pathogenesis of septic shock. Proinflammatory cytokines such as tumor necrosis factor-alpha (TNF-alpha) and interleukin-1beta (IL-1beta) stimulate the progression of septic shock whereas the anti-inflammatory cytokine IL-10 has counterregulative potency. The amino acid glycine (GLY) has been shown to protect against endotoxin shock in the rat by inhibiting TNF-alpha production. In the current study we investigated the role of GLY on lipopolysaccharide (LPS) -induced cell surface marker expression, phagocytosis, and cytokine production on purified monocytes from healthy donors. GLY did not modulate the expression of HLA-DR and CD64 on monocytes, whereas CD11b/CD18 expression (P<0.05) and E. coli phagocytosis (P<0.05) decreased significantly. GLY decreased LPS-induced TNF-alpha production (P<0.01) and increased IL-10 expression of purified monocytes. Similarly, in a whole blood assay, GLY reduced TNF-alpha (P<0.0001) and IL-1beta (P<0.0001) synthesis and increased IL-10 expression (P<0.05) in a dose-dependent manner. The inhibitory effects of GLY were neutralized by strychnine, and the production of IL-10 and TNF-alpha was augmented by anti-IL-10 antibodies. Furthermore, GLY decreased the amount of IL-1beta and TNF-alpha-specific mRNA. Our data indicate that GLY has a potential to be used as an additional immunomodulatory tool in the early phase of sepsis and in different pathophysiological situations related to hypoxia and reperfusion.     

变应性鼻炎患者外周血中IL-27和Treg细胞的相关性分析

目的探讨外周血IL-27和CD4^＋CD25^＋调节性T细胞（Treg）在变应性鼻炎（AR）发病机制中的作用。方法2012年3月至7月,收集AR患者32例（AR组）和20例健康志愿者（对照组）外周血,采用流式细胞术（FCM）检测外周血中Treg细胞比例;ELISA检测血清中IL-27、IL-10和TGF-β1的水平。结果AR组Treg细胞百分率[（1．75±0．56）％]明显低于对照组[（4．76±1．75）％],两组比较的差异有统计学意义（P〈0．01）。AR组IL-27、IL-10和TGF-β1的水平分别为（24．43±16．36）pg／ml、（14．29±6．16）pg／ml、（0．34±0．04）pg／ml,均低于对照组（44．09±13．12）pg／ml、（31．32±21．20）pg／ml、（O．49±0．06）pg／ml,两组之间的差异有统计学意义（P〈0．01）。AR患者外周血中IL-27和Treg细胞百分率、IL-10、TGF-β1存在正相关（r分别为0．825,0．646,0．517,P〈0．01）,Treg细胞百分率和IL-10、TGF-β1存在正相关（r=0.622,0．738,P〈0．01）,IL-10和TGF-β1无相关性（r=0．304,P〉0．05）结论AR患者外周血中IL-27水平降低,Treg细匏百分率降低及其主要分泌因子IL-10、TGF-β1水平降低,且IL-27与Treg细胞百分率、IL-10、TGF-β1水平呈正相关,提示在AR发病中IL-27对Treg细胞可能具有免疫调节作用。