姜黄素抑制脂多糖刺激的系膜细胞增殖及其白细胞介素1β和巨噬细胞趋化蛋白1基因的表达

目的　观察姜黄素对系膜细胞增殖以及对系膜细胞基质蛋白分泌的影响 ,并进一步探索姜黄素对系膜细胞白细胞介素 (IL 1β)和巨噬细胞趋化蛋白 (MCP 1)基因表达的改变。 方法　采用不同浓度姜黄素处理体外培养的人肾小球系膜细胞后 ,分别收集上清液及细胞 ,应用ELISA的方法测定上清液中胶原Ⅳ和Ⅲ的蛋白分泌量 ,MTT法测定系膜细胞活性 (吸光度值 ) ,RT PCR的方法测定系膜细胞IL 1β和MCP 1基因的相对表达量 ,以未加LPS及姜黄素和仅加LPS不加姜黄素作为对照组。结果　当姜黄素浓度大于或等于 6 2 5 μmol/L时 ,系膜细胞增殖明显受到抑制 (P <0 0 1) ,且表现为浓度依赖性。在基础状态下 ,系膜细胞分泌一定量的胶原Ⅳ和Ⅲ [(10± 9 13)ng/ml和 (2 9 5± 0 5 8)ng/ml],亦有MCP 1mRNA表达 [(42 1± 14 98) % ],但IL 1βmRNA几乎不表达 ;经LPS刺激后其胶原Ⅳ和Ⅲ分泌增加 [(138 75± 2 3 2 3)ng/ml和 (38 2 5± 5 38)ng/ml],同时IL 1β和MCP 1基因表达上调 [分别为 (16 91± 1 6 8) %和 (76 6± 6 5 9) % ],而姜黄素浓度为 4 μmol/L时即能明显抑制LPS刺激的系膜细胞胶原Ⅳ和Ⅲ的蛋白分泌 (P <0 0 5 ) ,且在高浓度时作用更为明显 ;同时姜黄素还能消除LPS上调系膜细胞IL 1β和MCP 1基因表达的作用 (P <     

二价金属离子转运蛋白-1和膜铁转运蛋白-1在不同铁状态孕妇胎盘中的表达

目的 测定二价金属离子转运蛋白-1(DMT1) mRNA剪切异构体和膜铁转运蛋白-1(FPN1) mRNA在不同铁状态足月孕妇胎盘中的表达水平,探讨胎盘铁转运及调控机制.方法 选择在郑州大学第一附属医院产科分娩的无高血压、糖尿病、感染、肿瘤、肝炎的足月孕妇69例,其中14例Hb＜100 g/L及血清铁蛋白(SF)≥12 μg/L者排除,符合条件者55例.根据母血Hb、血清铁(SI)、SF将孕妇分为3组:正常组(N组)23例,Hb≥100 g/L,SF≥12 μg/L;铁缺乏组(ID组)20例,Hb≥100 g/L,SF＜12 μg/L;轻度缺铁性贫血组(IDA组)12例,90 g/L≤Hb＜100 g/L,MCV＜80 fL,MCH＜27 pg,MCHC＜320 g/L,SF＜12 μg/L,SI＜8.95 μmol/L;采用血细胞自动计数仪测定其血常规,比色法测定其SI,放射免疫分析法测定其SF.采用反转录-PCR技术检测胎盘组织DMT1 mRNA剪切异构体及FPN1 mRNA表达水平.结果 1.N组、ID组及IDA组含铁反应元件的二价金属离子转运蛋白-1(DMT1-IRE) mRNA分别为(0.568 2±0.116 9)、(0.709 0±0.138 9)、(0.912 8±0.179 8),3组间比较差异有统计学意义(F=23.955 P＜0.01),两两比较亦有统计学意义(Pa＜0.01).2.N组、ID组及IDA组不含铁反应元件的二价金属离子转运蛋白-1(DMT1-nonIRE mRNA)分别为(0.738 0±0.224 0)、(0.806 1±0.212 8)、(0.766 7±0.210 8),3组间比较差异无统计学意义(F=0.562 P＞0.05);3.N组、ID组及IDA组FPN1 mRNA分别为(0.462 5±0.077 6)、(0.507 1±0.074 4)、(0.551 8±0.104 1),3组间比较差异有统计学意义(F=4.767 P＜0.05),其中IDA组与N组比较差异有统计学意义(P＜0.01),而ID组与N组、ID组与IDA组比较差异均无统计学意义(Pa>0.05).结论 ID及IDA孕妇可通过上调胎盘DMT1-IRE mRNA、FPN1 mRNA的转录最大限度的增加了母体血浆铁至胎儿的转运,以保证胎儿铁供给的相对恒定.     

白细胞介素-1受体拮抗剂对NZB/WF_1小鼠狼疮肺损害防治作用的研究

目的　探讨白细胞介素 1受体拮抗剂 (IL 1ra)在狼疮性肺损害防治中的价值。方法对有狼疮倾向的NZB/WF1小鼠腹腔内注射生理盐水和IL 1ra,对比观察其对细胞因子活性和肺部病理形态学改变的影响。结果　实验组和对照组IL 2活性分别为 (2 3± 4)U/ml和 (18± 3)U/ml(P <0 .0 5 ) ;NK细胞活性分别为 (76± 2 1) %和 (45± 4) % (P <0 .0 5 ) ;IL 1α分别为 (173± 78)pg/ml和 (44 2±10 0 )pg/ml(P <0 .0 1)。对照组小鼠肺组织病理变化重 ,表现为细支气管及小血管周围重度慢性炎性细胞浸润 ,毛细血管扩张充血 ,肺泡间质明显增厚及纤维化 ,而实验组小鼠毛细支气管和小血管周围炎性细胞浸润、毛细血管扩张 ,以及肺泡间质增厚均较对照组明显为轻。结论　IL 1ra在预防和治疗系统性红斑狼疮所致的肺损害方面有较好的效果。     

用多肽核酸提高β地贫患者γ珠蛋白基因表达

目的 　观察与人γ珠蛋白基因互补的多肽核酸 (PNAs)对红系干 /祖细胞中珠蛋白基因表达的影响。方法 　合成可与人γ珠蛋白基因 - 1 86区结合的多肽核酸 ,加载反向载体肽。二步法进行外周血红系干 祖细胞的液体培养 ,于第二步培养的第6天加入PNA 0、1 5、30 μmol L。于第二步培养第 1 2天结束培养 ,提取细胞总RNA。RT -PCR进行cDNA合成和目的片段的扩增 ;进行PCR产物分析。结果 　PNAs对正常人及 β地贫患者体外培养红系细胞珠蛋白的 β/αmRNA比值无明显影响 (P >0 0 5) ;PNA 1 5、30 μmol L均可使正常人和β地贫患儿外周血体外培养红系细胞珠蛋白γ/αmRNA、非α/αmRNA的比值提高 (P <0 0 1 ) ,且 1 5、30 μmol L浓度之间比较有明显差异 (P <0 0 1 )。结论 　PNAs能促进体外培养红系细胞γ珠蛋白基因转录。     

生长因子β1对儿童哮喘的作用及孟鲁司特钠对其影响

目的 探讨生长因子β1在儿童哮喘中的作用及观察孟鲁司特钠对其的影响。方法 筛选2009年9月-2010年9月我院哮喘专病门诊轻度持续哮喘患儿60例及来院健康体检儿童30例,将哮喘患儿随机分成孟鲁司特钠组和安慰剂对照组;采用双抗夹心酶联免疫吸附试验( ELISA)、RT-PCR技术分别检测治疗前后患儿血浆中TGF-β1水平和外周血单个核细胞(PBMC)中TGF-β1mRNA表达;采用流式细胞技术,检测表达叉状头/翅膀状螺旋转录因子3的CD4T调节细胞(Foxp3+ CD4+ Treg)及各亚型的比例。结果 (1)血浆中TGF-β1水平：治疗前哮喘组[(11.51±1.12) ng/L]明显低于健康对照组[(47.92±1.52) ng/L](q=20.01,P＜0.01);治疗后,孟鲁司特钠组[ (20.03±1.14)ng/L]高于安慰剂组[(12.10±3.91) ng/L]（q=14.62,P＜0.05）,但均值仍低于健康对照组;(2)外周血单个核细胞中TGF-β1 mRNA表达：治疗前哮喘组(0.31 +0.07)明显低于健康对照组(0.61±0.2) (q =8.97,P＜0.05);治疗后,孟鲁司特钠组(0.46±0.13)表达高于安慰剂组(0.32±0.04)（q=8.25,P＜0.05）,但仍低于健康对照组;(3)流式细胞检测结果各组间比较差异有统计学意义(P＜0.05)：哮喘患儿与健康对照组相比,Foxp3+ CD4+ Treg细胞比例增加[(8.30±1.30)％,(6.05±1.80)％];其中CD45 RA+ Foxp3lo比例增高[(4.60±1.04)％,(3.27±1.03)％];CD45 RA - Foxp3h1比例降低[(0.75±0.13)％,(0.93±0.26)％];CD45 RA-Foxp3lo比例两组差异无统计学意义。治疗后,孟鲁司特钠组较安慰剂组,aTreg细胞占Foxp3+ CD4+ Treg比例增加[(1.16±0.24)％,(0.89±0.22)％],差异有统计学意义。结论哮喘儿童体内存在血浆及外周血单个核细胞中TGF-β1表达的降低,可能是导致哮喘发病的重要原因;孟鲁司特钠能有效改善TGF-β1的表达并通过调节Foxp3的表达来发挥治疗作用。     

转化生长因子-β1诱导新生大鼠肺成纤维细胞增殖的细胞周期调控研究北大核心CSCD

目的探讨转化生长因子（TGF）-β1刺激下细胞周期调控对肺成纤维细胞增殖的影响,了解支气管肺发育不良（BPD）的发病机制。方法对出生1 d新生大鼠的肺成纤维细胞进行分离、纯化和鉴定,将原代肺成纤维细胞经TGF-β1刺激后,应用免疫组织化学及Western blot技术检测周期蛋白依赖性激酶-2（CDK2）及p27的蛋白表达情况,实时荧光定量PCR检测CDK2及p27的mRNA表达,并同时应用CCK8试剂盒检测细胞增殖,流式细胞仪检测细胞周期的变化。结果对鉴定后的新生大鼠肺成纤维细胞进行TGF-β1刺激后,可以观察到原代成纤维细胞的CDK2蛋白及mRNA表达增加,并伴p27蛋白及mRNA水平下降;CCK8显示吸光度值增高,增殖明显,S期细胞所占比例同时增加,G0/G1期逐渐减少。0、10 μg/L的TGF-β1刺激后S期细胞所占比例分别为4.63%、67.09%,G0/G1期为83.67%和67.09%。10 μg/L的TGF-β1刺激12 h和48 h后S期细胞所占比例分别为7.64%、9.11%,G0/G1期为73.99%和59.81%。随着TGF-β1水平增加（0 μg/L、5 μg/L及10 μg/L）,CDK2蛋白及mRNA表达进一步增加;并且相同水平TGF-β1刺激,随着时间的延长（10 μg/L的TGF-β1刺激12、24、48 h）,CDK2蛋白及mRNA表达进一步增加,48 h较对照组增加显著（P〈0.05和〈0.01）,p27蛋白及mRNA水平随之进一步下降,48 h较对照组增加显著（均P〈0.01）。结论TGF-β1能够使新生大鼠肺原代成纤维细胞CDK2/p27表达失衡,加速细胞周期进程,使成纤维细胞过度增殖。     

过敏性紫癜患儿急性期血浆转化生长因子-β1和血管内皮生长因子检测及其临床意义

目的　探讨过敏性紫癜 (HSP)患儿急性期血浆转化生长因子 β1(TGF β1)和血管内皮生长因子(VEGF)的水平变化及其在HSP发病机制中的作用和临床意义。方法　采用双抗体夹心酶联免疫吸附法检测2 0 0 1年 10月至 2 0 0 2年 12月青岛大学医学院附属医院儿科收治的 38例急性期HSP患儿、16名正常健康儿童血浆TGF β1和VEGF水平 ,并检测其中 2 0例HSP患儿外周血单个核细胞 (PBMC)培养上清液TGF β1水平。结果　 ( 1)HSP患儿急性期血浆TGF β1水平明显高于对照组 (P <0 0 1) ;HSP患儿和对照组血浆TGF β1水平与PBMC体外诱生TGF β1水平均呈正相关 ( r=0 6 5 ,0 5 7;P <0 0 1,P <0 0 5 )。 ( 2 )HSP患儿急性期血浆VEGF水平明显高于对照组 (P <0 0 1) ;有胃肠道症状患儿血浆VEGF水平明显高于无胃肠道症状患儿 (P <0 0 5 )。 ( 3)HSP急性期血浆TGF β1和VEGF水平呈正相关 (r =0 5 1,P <0 0 5 )。结论　HSP患儿急性期血浆TGF β1和VEGF水平明显升高 ,二者参与了HSP免疫与血管炎症反应过程 ,均为体内保护性反应。     

Hp感染儿童胃十二指肠粘膜IL-8及IL-8 mRNA的研究

目的　检测Hp感染儿童胃、十二指肠粘膜中IL 8及IL 8mRNA的变化 ,从蛋白和分子水平探讨Hp对细胞因子IL 8的影响 ,以及IL 8在Hp相关性胃十二指肠疾病中的作用。方法　胃镜下取胃窦及十二指肠粘膜活检标本 ,用ELISA法和RT PCR半定量法测定胃及十二指肠粘膜中IL 8的含量和IL 8mRNA的表达量。结果　Hp阳性者胃粘膜IL 8为 2 4 66～ 177 77pg/mg ,IL 8mRNA为2 3 7～ 4 99;Hp阴性者胃粘膜IL 8为 2 94～ 12 98pg/mg,IL 8mRNA为 0 0 5～ 0 44 ;差异有显著意义(t分别为 12 3 4和 2 9 2 9,P <0 0 1)。Hp阳性者十二指肠粘膜IL 8为 12 98～ 177 77pg/mg ,IL 8mRNA为 1 2 2～ 1 80 ;Hp阴性者十二指肠粘膜IL 8为 2 0 4～ 10 43pg/mg ,IL 8mRNA为 0 0 1～ 0 2 3 ;差异有显著意义 (t分别为 7 18和 3 7 2 0 ,P <0 0 1)。活动性胃炎胃粘膜IL 8为 12 98～ 177 77pg/mg,IL 8mRNA为 0 5 1～ 4 99;非活动性胃炎胃粘膜IL 8为 2 0 4～ 10 43pg/mg,IL 8mRNA为 0 0 1～ 0 44 ;差异有显著意义 (t分别为 10 66和 18 62 ,P <0 0 1)。活动性胃炎十二指肠粘膜IL 8为 5 2 8～ 47 76pg/mg ,IL 8mRNA为 0 2 3～ 1 87;非活动性胃炎十二指肠粘膜IL 8为 3 19～ 8 14pg/mg,IL 8mRNA为0 0 1～ 0 2 0 ;差异有显著意义 (     

血、尿β2-微球蛋白在糖尿病肾病诊断中的临床意义

目的　探讨血、尿 β2 微球蛋白 (β2 MG)检测对发现早期糖尿病肾病的临床意义。方法　用放射免疫法对糖尿病组患儿和正常对照组儿童血、尿 β2 MG进行定量测定。结果　糖尿病组患儿血 β2 MG(32 15±110 0 ) μg/L ,尿 β2 MG(4 16± 2 91) μg/L ;对照组血 β2 MG(190 8± 85 2 ) μg/L ,尿 β2 MG(178± 12 9) μg/L ,两组比较均有显著性差异 (P均 <0 .0 5 ) ;糖尿病病程 <5年组血 β2 MG (2 6 0 4± 910 ) μg/L ,尿β2 MG(386± 2 91) μg/L ;>5年组血β2 MG(3415± 136 1) μg/L ,尿 β2 MG(10 12± 94 5 ) μg/L ,两组比较有显著性差异 (P均 <0 .0 5 )。 结论　血、尿 β2 MG是发现早期糖尿病肾病的敏感指标     

肺炎患儿血清β_2-微球蛋白及白细胞介素-2水平变化

目的　探讨小儿肺炎时免疫功能的变化。方法　采用放射免疫分析法测定 12 8例肺炎患儿血清β2 微球蛋白 (β2 MG)及白细胞介素 2 (IL 2 )水平 ,并与 38例健康儿童相比较。结果　轻、重型肺炎血 β2 MG水平分别为 (3.0 8± 0 .72 )mg/L ,(3.5 6± 0 .5 3)mg/L ,明显高于对照组 (1.83± 0 .5 7)mg/L ,P <0 .0 1;IL 2水平分别为 (2 .13± 0 .84)ng/L ,(1.95± 0 .79)ng/L较对照组 (5 .31± 1.2 4)ng/L显著降低 ,P <0 .0 1。结论　肺炎患儿细胞免疫功能较健康儿童低下。     

黄芪对IgA肾病模型大鼠免疫紊乱调节作用的研究

目的 探讨黄芪对IgA肾病(IgAN)模型大鼠免疫紊乱的调节作用.方法 采用口服牛血清白蛋白(BSA)、皮下注射四氯化碳(CCl4)加用尾静脉注射脂多糖(LSP)复合方法,复制IgAN模型大鼠.实验分为3组:正常组、模型组和黄芪治疗组;黄芪治疗组给予黄芪颗粒剂灌胃,正常组及模型组分别灌注等量蒸馏水.检测各组大鼠血尿、蛋白尿及肾脏病理改变,采用免疫组织化学技术检测各组大鼠肾组织中Th2类细胞因子转化生长因子β1(TGF-β1)、白细胞介素5(IL-5)表达情况,ELISA法检测血清中Th1类细胞因子干扰素γ(IFN-γ)和Th2类细胞因子白细胞介素4(IL-4)的水平.结果 ①IgAN模型组大鼠尿红细胞计数高于正常组和黄芪治疗组(P＜0.01);而IgAN模型组大鼠24 h蛋白尿亦高于正常组(P＜0.05)和黄芪治疗组(P＜0.05).②IgAN模型组大鼠肾小球系膜区、肾小管、肾间质病理损害较正常对照组和黄芪治疗组明显加重;模型组大鼠肾小球系膜区IgA免疫荧光较正常组和黄芪治疗组明显增强.③免疫组化结果显示,正常组肾组织有少量TGF-β1和IL-5表达,而IgAN模型组大鼠肾组织中TGF-β1和IL-5表达明显增强,与正常对照组和黄芪治疗组TGF-β1(P＜0.05)和IL-5(P＜0.05)比较差别有统计学意义.④模型组大鼠血清IL-4含量[(33.74±7.52)pg/ml]显著升高,与正常对照组[(2.36±0.85)pg/ml]和黄芪治疗组[(3.24±1.13)pg/ml]比较差别有统计学意义(P＜0.05);而模型组大鼠IFN-γ水平[(18.79±3.80)pg/ml]显著下降,与正常组[(46.53 ±5.56)pg/ml]和黄芪治疗组[(41.28±2.95)pg/ml]比较差别有统计学意义(P＜0.05).结论 黄芪可降低IgAN模型大鼠血尿和24 b蛋白尿水平,减轻肾脏病理变化及IgA在肾小球系膜区的沉积.可能的机制是通过调节IgAN模型大鼠Th1、Th2平衡紊乱,从而改善血清中Th类细胞因子IL-4和IFN-γ的水平,并减少肾组织中Th2类细胞因子TGF-β1和IL-5的表达,来延缓IgAN的发生发展.     

Correlation of interleukin-1 beta and cachectin concentrations in cerebrospinal fluid and outcome from bacterial meningitis

Because interleukin-1 beta (IL-1 beta) and cachectin (tumor necrosis factor) are thought to mediate the body's response to microbial invasion, we measured IL-1 beta and tumor necrosis factor concentrations in paired cerebrospinal fluid (CSF) samples (on admission to the hospital, CSF1; 18 to 30 hours later, CSF2) from 106 infants and children with bacterial meningitis. In CSF1, IL-1 beta was detected in 95% of samples; the mean (+/- 1 SD) concentration was 944 +/- 1293 pg/ml. Patients with CSF1 IL-1 beta concentrations greater than or equal to 500 pg/ml were more likely to have neurologic sequelae (p = 0.001). Tumor necrosis factor was present in 75% of CSF1 samples; the mean concentration was 787 +/- 3358 pg/ml. In CSF2 the mean IL-1 beta concentration was 135 +/- 343 pg/ml, and IL-1 beta concentrations correlated significantly with CSF2 leukocyte count, with glucose, lactate, protein, and tumor necrosis factor concentrations, and with neurologic sequelae. Tumor necrosis factor was detected in CSF2 specimens of 53 of 106 patients, with a mean concentration of 21 +/- 65 pg/ml. Of the 106 patients, 47 received dexamethasone therapy at the time of diagnosis. These patients had significantly lower concentrations of IL-1 beta and higher glucose and lower lactate concentrations in CSF2, and they had a significantly shorter duration of fever compared with the values in patients not treated with steroids (p less than or equal to 0.002). Our data suggest a possible role of IL-1 beta and tumor necrosis factor as mediators of meningeal inflammation in patients with bacterial meningitis, and might explain, in part, the beneficial effect of dexamethasone as adjunctive treatment in this disease.     

Effect of hypoxia on renal prostaglandin E2 production in human and rat neonates.

Effect of hypoxia on renal prostaglandin E2 (PGE2) production was shown in asphyxic newborn infants and experimental hypoxic rats. In asphyxic infants, at postnatal day 1, the urinary excretion of PGE2 in severe asphyxia (1.00 +/- 0.19 pg/kg/min, n = 10) was lower than that of the mild asphyxia (2.15 +/- 0.18 pg/kg/min, n = 10) or normal newborn infants (2.65 +/- 0.25 pg/kg/min, n = 8) (p less than 0.01). The urinary excretion of PGE2 was inversely correlated with the urinary N-acetyl-beta-D-glucosaminidase (r = -0.84, p less than 0.01). The urine volume in mild asphyxia (0.04 +/- 0.005 ml/kg/min) was higher in comparison to normal newborn infants (0.026 +/- 0.002 ml/kg/min) (p less than 0.01), but had no correlation with the urinary excretion of PGE2. In experimental hypoxic rats, the renal PGE2 concentration increased from 0.19 +/- 0.02 ng/mg protein to the maximum level of 0.59 +/- 0.03 ng/mg protein at 10 min of hypoxia. The renal PGE2 concentration then decreased to the minimum level (0.105 +/- 0.02 ng/mg protein) at 24 h after 20 min hypoxia. The renal ATP rapidly decreased during 20 min hypoxia, and gradually increased to 55.1 +/- 6.2 nmol/mg protein at 24 h after 20 min hypoxia, which recovered only about 60% of the control level. It seems likely that renal PGE2 does not play a major role in diuresis in mild birth asphyxia and that severe birth asphyxia suppresses the renal PGE2 production in early neonatal period.(ABSTRACT TRUNCATED AT 250 WORDS)     

Middle ear effusion IL-6 concentration in bacterial and non-bacterial acute otitis media

BACKGROUND: The pathogenesis of acute otitis media is complex and multifactorial. It is characterized by inflammation of the middle ear with an infiltration of leukocytes, macrophages and mast cells. The resulting effusion contains a large amount of inflammatory mediators, among which are cytokines. OBJECTIVES: To test the role of IL-6 in the inflammatory process associated with acute otitis media. METHODS: We analyzed 20 middle ear fluid (MEF) sample pairs, obtained by aspiration before initiating antibiotic therapy (day 1) and during treatment (days 4-5), for the presence of IL-6. IL-6 concentrations were assayed with an ELISA kit (detection limit 5 pg/ml) and were correlated with bacterial etiology and bacterial eradication from the middle ear. RESULTS: IL-6 was detected in all middle ear effusions analyzed. We found decreased IL-6 concentrations in culture negative MEF compared to culture positive MEF on both days I and 4-5 (day 1, 1752.20+/-1001.31 pg/ml vs 1216.20+/-1015.44 pg/ml, p = 0.19; days 4-5, 1049.36+/-472.40 pg/ml vs 800.33+/-676.00 pg/ml, p = 0.23); however, differences did not achieve statistical significance. Overall, a marked and significant decrease in IL-6 concentration occurred following 72-96 h of antibiotic therapy (1618.15+/-1004.88 pg/ml vs 936.85+/-581.05 pg/ml, p = 0.04). While MEF IL-6 concentrations decreased in ears where bacteria persisted (1468.20+/-858.48 pg/ml vs 1044.80+/-514.16 pg/ml, p = 0.167) or were eradicated (2320.20+/-866.16 pg/ml vs 767.40+/-522.88 pg/ml, p = 0.029), a more prominent decline was demonstrated in the latter. CONCLUSIONS: These results strongly suggest the involvement of IL-6 in the ongoing inflammatory process in both bacterial and non-bacterial acute otitis media. Resolution of inflammation in the middle ear, especially where bacteria were eradicated, is reflected by low IL-6 levels.     

Neonatal interleukin-1 beta, interleukin-6, and tumor necrosis factor: cord blood levels and cellular production

In a prospective study, levels of interleukin-1 beta (IL-1 beta), interleukin-6) (IL-6), and tumor necrosis factor (TNF) were measured in a blind fashion in cord blood plasma from 92 neonates by specific immunoassays, and were correlated with the clinical courses of the infants, including type of delivery and perinatal complications. Plasma IL-1 beta concentration was undetectable in infants born by normal vaginal delivery or elective cesarean section but was significantly increased in infants born after induced vaginal deliveries (142 +/- 68 pg/ml) or urgent cesarean section (290 +/- 21 pg/ml; both p less than 0.05 compared with normal deliveries). The IL-1 beta levels were elevated in infants with severe perinatal complications (282 +/- 116 pg/ml; p less than 0.001), whereas TNF and IL-6 levels were not related to these complications. Infants with isolated perinatal infectious complications had elevated levels of plasma IL-6 compared with those of sick neonates without infection (p less than 0.001). In contrast, TNF plasma levels and IL-1 beta production by cord blood leukocytes were decreased in infants with infectious complications alone (both p less than 0.05). These studies suggest that the levels of IL-1 beta, IL-6, and TNF in the cord plasma relate differentially to clinical complications in the perinatal period.     

Cytokines (IL-1beta, IL-6, TNF-alpha, TGF-beta1, and TGF-beta2) and prostaglandin E2 in human milk during the first three months postpartum.

Postpartum changes in the concentrations of IL-1beta, IL-6, tumor necrosis factor-alpha (TNF-alpha), transforming growth factor-beta1 (TGF-beta1), TGF-beta2, and prostaglandin E2 in 257 human milk samples collected longitudinally from 49 healthy mothers during the first 12 wk of lactation were determined by ELISA or RIA. The proinflammatory cytokines IL-1beta, IL-6, and TNF-alpha were present in only a proportion of samples, and there was a wide range of concentrations detected at each time in the present study (IL-1beta, <15-400 pg/mL; IL-6, <15-1032 pg/mL; TNF-alpha, <15-2933 pg/mL). Concentrations of prostaglandin E2 increased after the first week and remained elevated for the remainder of the study (range, < 10-9966 pg/mL). The antiinflammatory cytokines TGF-beta1 (range, 43-7108 pg/mL) and TGF-beta2 (range, 208-57935 pg/mL) were present in substantial quantities in all samples, and there was little change in the mean concentration during 12 wk of lactation. The present study shows that immunomodulating agents are normally present in human milk in physiologically relevant quantities for at least the first 3 mo of the breast-fed infant's life.     

Different proinflammatory reactions in fatal and non-fatal enterovirus 71 infections: implications for early recognition and therapy

AIM: The mechanism of pulmonary oedema, a life-threatening manifestation of enterovirus 71 (EV71) encephalitis, is unclear. Our aim was to assess the relationship of proinflammatory cytokines to EV71-related pulmonary oedema. METHODS: Proinflammatory responses in 33 EV71 patients with various complications and 21 normal healthy children were measured using an enzyme-linked immunosorbent assay. RESULTS: EV71 patients with both encephalitis and pulmonary oedema were found to have much higher levels of blood interleukin-6 (IL-6) (947 +/- 1239 vs 4.9 +/- 3.1 pg/ml, p = 0.0003), tumour necrosis factor-alpha (TNF-alpha) (22.4 +/- 29.5 vs 5.3 +/- 1.0 pg/ml, p = 0.0035), interleukin Ibeta (IL-1beta) (48.4 +/- 85.2 vs 4.9 +/- 10.1 pg/ml, p = 0.01), white blood cell count (28.3 +/- 7.6 vs 15.5 +/- 6.8 10(9)/L, p > or = 0.0001) and blood glucose (501 +/- 186 vs 165 +/- 117 mg/dL, p = 0.0009) than patients with EV71 encephalitis alone. In fact, the cytokine levels in patients with encephalitis only or in those without complications were not significantly different from the levels found in normal children. The sensitivity, specificity, positive and negative predictive values of IL-6 > 70 pg/ml for EV71 encephalitis with pulmonary oedema were all 100%. CONCLUSION: Patients with EV71-related encephalitis combined with pulmonary oedema were found to have significantly elevated levels of proinflammatory cytokines and the best predictor for this complicated condition was found to be the level of serum IL-6.     

High frequency oscillatory ventilation suppresses inflammatory response in lung tissue and microdissected alveolar macrophages in surfactant depleted piglets

The impact of high frequency oscillatory ventilation (HFOV) compared with intermittent mandatory ventilation (IMV) on oxygenation and pulmonary inflammatory response was studied in a surfactant depleted piglet model. After establishment of lung injury by bronchoalveolar lavage, piglets either received HFOV (n =5) or IMV (control; n = 5) for eight hours. PaO(2) was higher and mean pulmonary arterial pressure (MPAP) was lower with HFOV (HFOV versus control, mean +/- SEM; endpoint PaO(2): 252 +/- 73 versus 68 +/- 8.4 mm Hg; p < 0.001; MPAP: 22 +/- 2.3 versus 34 +/- 2.5 mm Hg; p < 0.01). mRNA expression of interleukin (IL)-1 beta, IL-6, IL-8, IL-10, TGF-beta 1, Endothelin-1, and adhesion molecules (E-selectin, P-selectin, ICAM-1) in lung tissue was quantified by real time PCR normalized to beta-actin and hypoxanthine-guanine-phosphoribosyl-transferase (HPRT). mRNA expression of all cytokines and adhesion molecules/HPRT was higher in controls (e.g.: HFOV versus control, mean +/- SEM; IL-1 beta/HPRT: 1.6 +/- 0.3 versus 23.1 +/- 8.6 relative units (RU), p < 0.001; IL-8/HPRT: 8.5 +/- 2.0 versus 63.5 +/- 15.2 RU, p < 0.001). IL-8/HPRT gene expression was quantified in microdissected single cells. With HFOV, IL-8 gene expression was highly reduced in alveolar macrophages: 10 +/- 3.4 copies IL-8 mRNA/copy HPRT mRNA versus 356 +/- 142; p < 0.05 (bronchiolar epithelial cells: 33 +/- 16 versus 208 +/- 108; alveolar septum: 2.1 +/- 1.3 versus 26 +/- 11; bronchiolar smooth muscle cells: 1.3 +/- 0.3 versus 2.8 +/- 1.0; vascular smooth muscle cells: 0.7 +/- 0.3 versus 1.1 +/- 0.4). In conclusion, HFOV improved oxygenation, reduced pulmonary arterial pressure and attenuated pulmonary inflammatory response.     

Interleukin-6 and interleukin-8 are elevated in the cerebrospinal fluid of infants exposed to chorioamnionitis

BACKGROUND: The clinical or histologic diagnosis of chorioamnionitis has been associated with an increased risk of neuropathology and adverse neurologic outcomes in premature and term infants. Inflammatory cytokines have been implicated in the pathogenesis of these processes. The objective of this study was to determine whether exposure to chorioamnionitis and fetal inflammatory syndrome is associated with elevated concentrations of inflammatory cytokines (TNF-alpha, IL-6, and IL-8) in the CSF of term and preterm infants. METHODS: Eighty-four mother/infant pairs were studied, 54 infants were premature. Twenty-eight showed signs of maternal (n = 14), or fetal (n = 14) inflammation based on placental pathology; mothers of 24 infants showed signs of clinical chorioamnionitis not confirmed by placental pathology and 32 infants were considered as 'controls' since they had only transient difficulty adjusting to extra-uterine life warranting evaluation for sepsis. The cytokine concentrations in the CSF were measured within 24 h of birth. RESULTS: When compared to the control group (IL-8 = 341 +/- 170 pg/ml and IL-6 = 7.4 +/- 1.8 pg/ml) significantly higher concentrations of IL-8 were detected in the CSF of infants exposed to clinical chorioamnionitis (1,854 +/- 878 pg/ml; p = 0.001) and maternal/fetal inflammation (1,754 +/- 787 pg/ml; p = 0.001) and of IL-6 in infants with maternal/fetal inflammation (47.6 +/- 45.1 pg/ml; p = 0.01). CONCLUSIONS: These results indicate that infants exposed to clinical chorioamnionitis, or inflammation in utero, experience at least a transient elevation in inflammatory cytokines in CSF.