耐力训练对ApoE-/-致AS小鼠IL-18和IL-10表达的影响

目的：深入观察耐力训练对载脂蛋白E基因敲除（ApoE^-/-）致动脉粥样硬化（AS）小鼠白介素18（IL-18）和白介素10（IL-10）的影响,探讨运动防治AS的可能机制。方法：选取8周龄雄性ApoE^-/-小鼠20只：随机分为2组（n=10）：AS模型组（AC组）和运动干预组（AE组）,AE组进行跑台耐力训练;选取8周龄C57BL/6J雄性小鼠10只作为正常对照组（CC组）。实验持续12周,取主动脉制作冰冻切片,分别用于观察主动脉AS斑块和病理变化以及主动脉IL-18、IL-10蛋白表达;采用ELISA法检测血清IL-18、IL-10水平。结果：①12周高脂膳食致ApoE^-/-小鼠发生典型的AS病变,耐力训练使AS斑块面积显著减少（P<0.01）,病变程度显著减轻。②与CC组比较,AC组、AE组小鼠血清IL-18和IL-10水平均显著升高（P<0.01）,且AC组IL-18/IL-10比值显著升高（P<0.01）。AE组血清IL-18水平及IL-18/IL-10比值均显著低于AC组（P<0.01）。③与CC组比较,AC组、AE组小鼠主动脉IL-10和IL-18蛋白表达均显著升高（P<0.01）,AE组IL-10表达显著高于AC组（P<0.05）,IL-18表达显著低于AC组（P<0.05）。结论：耐力训练通过降低血液和主动脉IL-18及提高IL-10水平,增强了主动脉血管抗炎能力,从而发挥抗AS的作用。     

有氧运动联合黑果枸杞对高脂膳食大鼠心肌脂代谢某些指标的影响*

目的: 研究有氧运动联合黑果枸杞对高脂膳食大鼠心肌脂代谢某些指标的影响。方法: 55只雄性Wistar大鼠经过适应性饲养4 d后进行20 min/d的无负重游泳训练,连续3 d,筛选淘汰5只不适应游泳训练的大鼠后,按体重以数字随机分组法分为5组:普通膳食+安静组(RDC组)、高脂膳食+安静组(HDC组)、高脂膳食+黑果枸杞+安静组(HDLC组)、高脂膳食+有氧运动组(HDM组)、高脂膳食+黑果枸杞+有氧运动组(HDLM),每组10只。HDM组和HDLM组进行6周每周6次60 min/d的无负重游泳训练。RDC组大鼠以普通饲料常规喂养;其余各组以高脂饲料喂养;HDLC组和HDLM组大鼠灌胃黑果枸杞,灌胃剂量为4.48 g/(kg·d),灌胃体积为5 ml/kg,其余各组灌胃等量蒸馏水。6周后,测定大鼠Lee’s指数,取血、心肌检测相关生化指标。结果: 与RDC组比较,HDC组Lee’s指数,血清FFA、TNF-α、IL-6、TC、TG、LDL-C,心肌FFA、ICAM-1显著升高(P＜0.01);血清HDL-C水平显著降低(P＜0.01)。与HDC组比较,HDLC、HDM、HDLM组Lee’s指数,血清FFA、TNF-α、IL-6、TC、TG、LDL-C,心肌FFA、ICAM-1显著降低(P＜0.05或P＜0.01);血清HDL-C水平显著升高(P＜0.05或P＜0.01)。与HDLC、HDM组比较,HDLM组Lee’s指数,血清FFA、TNF-α、IL-6、TC、TG、LDL-C,心肌FFA、ICAM-1显著降低(P＜0.05);血清HDL-C水平显著升高(P＜0.05)。结论: 有氧运动和/或黑果枸杞干预能够不同程度改善高脂膳食大鼠脂代谢,降低肥胖引发的脂毒性。其中联合干预较单一干预更为有效。     

前列解毒活血汤对Ⅲ型前列腺炎患者前列腺液中细胞因子水平的影响*

目的: 探讨前列解毒活血汤对Ⅲ型前列腺炎患者前列腺液(EPS)中肿瘤坏死因子(TNF-α)、白介素-6(IL-6)及白介素-8(IL-8)的影响。方法: 将60例病患随机分成两组,即治疗组30例病患,对照组30例病患。治疗组患者每日早、晚饭后30 min温服150 ml前列解毒活血汤,对照组患者睡前30 min服用0.2 mg盐酸坦索罗辛缓释胶囊(哈乐),每日一次;另外选择30例健康男性作为空白组,不予任何处理。治疗周期为4周。治疗组、对照组患者干预前、后均要取EPS;空白组受试者只在临床干预实验进行前取一次EPS。酶联免疫吸附试验(ELISA)测定EPS中TNF-α、IL-6及IL-8含量或水平。结果: 实验开始前,治疗组、对照组患者观察值比较无差异,但与空白组比,数值显著升高(P＜0.01)。经有效干预后,治疗组、对照组患者的观察值均下降,治疗组下降趋势优于对照组(P＜0.01)。结论: 前列解毒活血汤能有效降低Ⅲ型前列腺炎患者EPS中TNF-α、IL-6及IL-8水平。     

大鼠双下肢骨折合并失血对心肌细胞损伤的作用及其机制

目的：探讨双下肢骨折创伤失血反应可否诱导心肌细胞发生凋亡反应,为深入研究骨折创伤后心肌损伤机制奠定基础。方法：SD大鼠20只,随机分为对照组及创伤组（n=10）,制备双下肢骨折创伤失血模型;原代心肌细胞培养复制创伤模型。ELISA检测血清IL-2、IL-6、IL-10、TNF-α水平;心肌组织HE染色、Tunel试验观察心肌受损、凋亡;Western blot及RT-PCR检测心肌组织凋亡调控基因Bcl-2/Bax表达变化。结果：创伤后血清炎性因子时间依赖性改变,IL-2（8 h）、IL-6、IL-10（4 h）、TNF-α（1 h）达到峰值,随后逐步回落;心肌HE染色发现心肌细胞肿大,排列紊乱,炎细胞浸润;Tunel试验证实大量核染成棕褐色的心肌细胞,凋亡指数增加（P<0.05）;Western blot及RT-PCR检测表明,无论在体及心肌细胞培养中,促凋亡基因Bax表达上调（P<0.05）,而抑凋亡基因Bcl-2表达下调（P<0.05）。结论：大鼠双下肢骨折创伤失血反应通过诱导心肌细胞凋亡进而造成心肌损伤。     

不同运动方式对肥胖大鼠肝脏脂质沉积及FGF21分泌的影响*

目的: 研究持续性运动训练(CT)与高强度间歇运动训练(HIIT)对正常和肥胖大鼠血清和肝脏FGF21蛋白含量及肝脏脂肪代谢的影响。方法: 雄性SD大鼠随机分为两组:普通饲料及45%高脂饲料喂养,8周后以普通饲料喂养,大鼠体重增加20%为肥胖造模成功标准。将正常大鼠随机分为正常安静组(LC)、正常高强度间歇运动训练组(LHI)、正常持续性运动训练组(LCT),肥胖大鼠随机分为肥胖安静组(OC)、肥胖高强度间歇运动训练组(OHI)及肥胖持续性运动训练组(OCT),每组10只,运动干预组大鼠进行8周不同方式负重游泳运动训练干预,末次运动干预间隔24 h后取血液检测血清炎症因子、FGF21水平,取肝脏组织检测脂质含量、脂代谢酶含量及FGF21表达水平。结果: 与LC组比较,OC组大鼠体重、血清炎症因子、肝脏甘油三酯(TG)含量显著增高(P＜0.05),LHI组肝脏TG含量显著降低,LCT组肝脏FGF21表达水平显著增高(P＜0.05)。与OC组比较,OHI组大鼠肝脏TG含量显著降低(P＜0.05),线粒体CPT-1β、β-HAD酶含量显著升高(P＜0.05),OCT组大鼠肝脏LPL、FAT/CD36酶含量显著增高,血清、肝脏FGF21水平均显著上升(P＜0.05)。结论: 两种运动方式均能降低正常、肥胖大鼠体重及肥胖大鼠肝脏脂质沉积现象,其中HIIT上调线粒体脂肪氧化水平,显著降低正常、肥胖大鼠肝脏TG含量,而CT通过提高正常、肥胖大鼠肝脏FGF21蛋白表达及血清FGF21水平,促进肝脏摄取脂肪酸,对缓解肥胖大鼠肝脏脂质沉积效果有限。     

持续与间歇重复跑台运动对大鼠空间学习记忆能力及海马BDNF基因表达的影响

目的：探讨中等强度持续与间歇重复跑台运动6周对大鼠学习记忆能力及海马内脑源性神经营养因子（BDNF）基因表达的影响。方法：将24只雄性SD大鼠随机分为3组（n=8）：空白对照（SC）组、持续训练（CT）组和间歇训练（IT）组。持续训练组以24 m/min的跑速持续运动30 min,训练频度每日1次;IT组与CT组运动强度和运动总时间相同,但IT组将30 min运动时间分为2个训练单位,每个单位15 min,两个训练单位间隔1 h,共训练6周。训练结束后,采用Morris水迷宫实验测试空间定位能力和探索能力。最后一次运动24 h后开颅取海马,QT-PCR法检测BDNF mRNA的表达水平。结果：①定位航行实验的结果表明,与SC组相比,IT组和CT组大鼠的逃避潜伏期显著缩短（P<0.01）,周围路程与周围时间均显著下降（P<0.05,P<0.01）,IT组与CT组之间无统计学差异。②空间探索实验的结果表明,与SC组相比,CT组和IT组站台中心路程均显著增加（P<0.05）,周围时间均显著减少（P<0.05,P<0.01）,但CT组和IT组组间相比无统计学差异;与SC组和CT组相比,IT组大鼠的潜伏期、站台周围时间均显著减少（P<0.05）。③QT-PCR结果显示,与SC组与CT组相比,IT组BDNF mRNA表达水平显著增高。结论：6周间歇重复跑台训练明显改善大鼠的空间学习记忆能力,这可能与这种类型运动更有利于促进海马BDNF基因的高表达有关。     

间歇运动对心梗大鼠心肌氧化应激和炎症的影响及其机制

目的: 探讨间歇运动激活心肌梗死(MI)大鼠SIRT1-Nox4-ROS通路抑制心脏氧化应激和炎症的作用。方法: 选取雄性SD 大鼠30 只,随机分为假手术对照(C)组,心肌梗死(MI) 组和心梗+间歇运动(ME)组,每组10 只。MI 组采用心脏左冠状动脉前降支(LAD) 结扎法,建立MI 模型。C组大鼠实施假手术,ME 组大鼠在MI 手术后1 周进行4 周跑台运动。第一周为适应性训练(10～15 m/min,30 min/d,共5 d)。正式训练起始训练速度10 m/min,时间为10 min。速度逐渐增至25 m/min,运动7 min后,间歇3 min,其速度为15 m/min,之后依次交替进行,运动总时间为60 min,5 d/周 ×4 周。训练结束后测定各组大鼠心电图变化,开胸摘取心脏。HE染色检测心肌组织结构,紫外分光光度法测定心脏MDA含量和SOD活性,微量酶标法测定心脏LDH活性,RT-qPCR 检测心肌SIRT1 mRNA表达,Western blot 检测心肌SIRT1、Nox4、TNF-α和IL-1β蛋白表达,DHE 法检测心肌活性氧(ROS)水平。结果: 与C组比较,MI组大鼠心肌组织出现代替性纤维化,心脏Nox4蛋白表达显著增加 (P＜0.01),MDA含量、LDH活性和ROS水平显著升高(P＜0.01),SOD活性显著降低 (P＜0.01),TNF-α和IL-1β蛋白表达显著增加 (P＜0.01),SIRT1 mRNA和蛋白表达显著降低 (P＜0.01)。与MI组比较,ME组大鼠心肌纤维化降低,心脏Nox4蛋白、MDA含量、LDH活性和ROS水平显著降低 (P＜0.01),SOD活性显著增强 (P＜0.01),TNF-α和IL-1β蛋白表达显著降低 (P＜0.01),SIRT1 mRNA和蛋白表达明显增多 (P＜0.01)。且发现SIRT1与Nox4及ROS 水平均呈显著负相关(r分别为-0.925和-0.899,P均＜0.01)。结论: 间歇运动抑制心梗心脏氧化应激和炎症反应,改善心功能,其机制与SIRT1-Nox4-ROS信号通路激活密切相关。     

PM2.5鼻腔滴注致小鼠海马组织损伤的炎性机制

目的: 探讨鼻腔滴注不同浓度的PM_2.5对小鼠海马组织损伤的炎性机制。方法: 30只C57BL/6J小鼠随机分为3组(n=10):对照组、低剂量组、高剂量组。采用鼻腔滴注方法进行染毒,每次染毒前测量体重,低剂量组和高剂量组PM_2.5染毒剂量分别为1.5 mg/kg BW和7.5 mg/kg BW,对照组给予等体积的生理盐水,隔天染毒一次,共12次。用ELISA法测定血清中肿瘤坏死因子-α(TNF-α)、白介素-1β(IL-1β)和白介素-6(IL-6)水平。HE染色和电镜观察肺和海马组织的病理变化及超微结构。用抗体芯片技术测定海马组织炎性细胞因子水平。结果: PM_2.5鼻腔滴注染毒对小鼠血清中TNF-α、IL-1β和IL-6水平无显著影响(P＞0.05),肺组织结构也无明显病理改变。而在海马组织中,低剂量和高剂量PM_2.5暴露均能导致海马CA3区神经元排列紊乱,并存在神经元细胞周围突触数量减少,小血管周围水肿等超微结构变化。利用抗体芯片检测海马组织炎性细胞因子表达变化,结果显示,与对照组比较,低剂量组海马组织中CX3CL1、CSF2和TECK等炎性细胞因子水平显著升高(P＜0.05),而MIG和sTNFR1显著降低(P＜0.05);高剂量组中炎性因子CX3CL1、CSF2和TCA-3等显著升高(P＜0.05),而Leptin、MIG和FASLG等显著降低(P＜0.05)。结论: PM_2.5鼻腔滴注可诱导小鼠海马组织结构损伤,其作用途径可能为嗅脑通路,引起海马损伤的炎性机制可能与TNF-α和IL-6等促炎因子的显著升高和sTNFR1 、FASLG等炎性疾病标志物的显著降低有关。     

游泳训练对高血压大鼠血压及血栓前状态分子的影响*

目的: 观察10周游泳训练对自发性高血压大鼠(SHR)血压及血栓前状态分子血管性血友病因子(vWF)、组织型纤溶酶原激活物(t-PA)、纤溶酶原激活物抑制物(PAI-1)的影响。方法: 选取10周龄雄性SHR(18只),随机分为对照组(8只)和训练组(10只),SHR训练组进行5次/周,每次60 min,共持续10周的无负重游泳训练,期间每2周测定大鼠血压。10周训练后,分别测定两组SHR血小板聚集率、血浆vWF、t-PA和PAI-1。结果: 与对照组相比,训练组SHR经4周游泳训练后,血压显著下降(P＜0.05),经10周游泳训练后,血压、血小板聚集率、血浆vWF水平、PAI-1活性显著降低(P＜0.01),血浆t-PA活性显著提高(P＜0.01)。结论: 适宜游泳训练能有效平抑(或改善)SHR的血压,坚持4周训练即可产生显著的作用,还可明显改善SHR血栓前状态,预防高血压血栓性并发症。     

姜黄素对视网膜缺血再灌注损伤大鼠IL-17、IL-23、IL-1β、TNF-α及NF-κB表达的影响

目的:研究不同剂量姜黄素对视网膜缺血再灌注损伤(RIRI)大鼠白细胞介素-17(IL-17)、白细胞介素-23(IL-23)、白细胞介素-1β(IL-1β)、肿瘤坏死因子-α(TNF-α)及核转录因子-κB(NF-κB)表达的影响。方法:选取60只健康的SPF级雄性SD大鼠,将大鼠随机分为正常对照组(NC组)、模型组(M组)、姜黄素低剂量组(LC组)和姜黄素高剂量组(HC组),均为15只。M组、LC组和HC组大鼠的右眼均利用前房灌注法制备成RIRI模型,NC组进行正常喂养。模型制备前30 min和造模成功后每日定时给LC组和HC组腹腔分别注射30 mg/kg和120 mg/kg的姜黄素进行干预,NC组和M组则在同一时间腹腔注射适量的生理盐水。建模72h后显微镜下观察四组大鼠视网膜的组织形态,采用酶联免疫吸附法检测四组大鼠视网膜组织中IL-17、IL-23、IL-1β和TNF-α的水平,利用免疫组化法分析四组大鼠视网膜组织中NF-κB的表达情况。结果:NC组大鼠视网膜组织形态正常,M组、LC组和HC组大鼠视网膜组织形态均呈现出不同程度的病理性损伤,损伤程度排序为HC组LC组M组。M组IL-17、IL-23、IL-1β和TNF-α水平均高于HC组、LC组和NC组,LC组IL-17、IL-23、IL-1β和TNF-α水平均高于HC组和NC组,而HC组高于NC组(P0.05)。M组NF-κB表达的OD值高于HC组、LC组和NC组,LC组NF-κB表达的OD值高于HC组和NC组,而HC组高于NC组(P0.05)。结论:RIRI与炎症反应的增强及NF-κB的激活有关,姜黄素可有效降低RIRI的炎性因子水平,抑制NF-κB的激活,从而减轻RIRI的病理损伤和保护视网膜,且其保护作用在一定范围内与姜黄素的剂量呈正相关。     

IL-23和IL-17在结核病中的研究进展

近年来结核病的发病率越来越高,随着对结核病免疫机制的进一步研究,发现了Th17、IL-23、IL-17在结核免疫保护中起着重要作用。对这免疫途径的研究有利于进一步阐明结核病的免疫机制和指导临床诊疗。     

IL-4 和IL-12 在宫颈癌中的表达及对紫杉醇过敏的影响

目的:研究IL-4,IL-12在宫颈癌组织中的表达,探讨其对宫颈癌发生及术后对紫杉醇过敏的影响。方法:应用半定量逆反应-聚合酶链反应(RT-PCR)技术检测IL-4mRNA,IL-12p35以及IL-12p40 mRNA在正常宫颈组和宫颈癌组中的表达,并分析两者之间的相关性以对紫杉醇过敏的影响。结果:1.宫颈癌组中IL-4mRNA表达水平高于正常宫颈组,而IL-12p35和IL-12p40mRNA表达低于正常宫颈组,差异有统计学意义(P<0.05);2.在术后给予紫杉醇治疗的宫颈癌患者中,过敏组中IL-4mRNA的表达高于不过敏组;IL-12p35和IL-12p40mRNA则低于后者,差异有统计学意义(P<0.05)。结论:体内IL-12降低和(或)IL-4升高可促进宫颈癌的发生发展增加紫杉醇过敏的发生率。     

蛇毒与细胞因子研究进展

全世界共有蛇类2500余种,其中毒蛇约650余种,估计每年被毒蛇咬伤的人数在30万以上,死亡率约为10％。我国蛇类有160余种,其中毒蛇约有50余种。剧毒、危害剧大的有10种,如眼镜蛇王、金环蛇、眼镜蛇、五步蛇、银环蛇、蝰蛇、蝮蛇、竹叶青、烙铁头、海蛇等,咬伤后能致人于死亡。我国两广地区蛇害严重,每年蛇咬伤的发病率约为25/10000。蛇毒的成分比较复杂．主要由蛋白质、多肽类和多种酶类组成。蛇毒对机体的作用比较复杂,按其有毒成分的毒理作用可分为神经毒、血循环毒和混合毒三类。银环蛇、金环蛇、海蛇的蛇毒主要含神经毒,其主要作用特点为通过多种不同的方式阻断神经一肌肉接头的冲动传递而导致呼吸肌麻痹,是蛇伤致死的主要原因;蝰蛇、五步蛇、烙铁头和竹叶青的蛇毒主要含血循环毒,包括心脏毒、凝血毒、溶血毒、蛋白水解酶、透明质酸酶等;眼镜王蛇等蛇毒属于混合毒,此类蛇毒既含神经毒成分,又含血循环毒成分。     

思连康治疗溃疡性结肠炎的疗效及机制研究

目的研究微生态制剂思连康辅助治疗溃疡性结肠炎的疗效及其可能的机制。方法将溃疡性结肠炎患者79例随机分成治疗组及对照组,治疗组40例,对照组39例。对照组采用常规治疗,治疗组在常规治疗的基础上加用双歧四联活菌制剂——思连康。比较2组治疗前及治疗2个月后患者的临床症状评分、结肠黏膜炎症表现、细胞因子IL-10、IL-18的变化。结果治疗2个月后2组临床症状评分、结肠黏膜炎症评分均较治疗前有明显改善（P〈0.01）,且治疗组临床症状、结肠黏膜炎症改善程度优于对照组（P〈0.01）,IL-10、IL-18的含量治疗前后有明显的变化,IL-10增加,IL-18降低。结论思连康可辅助治疗溃疡性结肠炎,其机制可能是通过调节细胞因子的变化,进一步影响结肠黏膜的免疫功能。     

Difference in response of NK cell activity in newborns and adult to IL-2, IL-12 and IL-15

The killing activity of cord blood mononuclear cells (cMNC) against cytomegalovirus (CMV)-uninfected and -infected fibroblasts was comparable to that of adult peripheral blood mononuclear cells (aPBMC). The killing activity of cMNC against K562 cells was significantly lower compared with that of aPBMC. Treatment of cMNC and aPBMC with interleukin-2 (IL-2), IL-12 or IL-15 significantly enhanced killing activity against K562 cells and CMV-uninfected and -infected cells. By comparison of cMNC with aPBMC, killing activity against the K562 cells of cMNC was augmented to the level of aPBMC when cultured with IL-2, IL-12 or IL-15. The killing activity of cMNC against CMV-uninfected and -infected fibroblasts did not increase to the level of adult PBMC by treatment with IL-2, IL-12 or IL-15. These data suggest that cord blood contains a functionally different NK cell subpopulation than that among adult NK cells.     

Potential role of myeloid cell/eosinophil-derived IL-17 in LPS-induced endotoxin shock

IL-17RA is a shared receptor subunit for several cytokines of the IL-17 family, including IL-17A, IL-17C, IL-17E (also called IL-25) and IL-17F. It has been shown that mice deficient in IL-17RA are more susceptible to sepsis than wild-type mice, suggesting that IL-17RA is important for host defense against sepsis. However, it is unclear which ligands for IL-17RA, such as IL-17A, IL-17C, IL-17E/IL-25 and/or IL-17F, are involved in the pathogenesis of sepsis. Therefore, we examined IL-17A, IL-17E/IL-25 and IL-17F for possible involvement in LPS-induced endotoxin shock. IL-17A-deficient mice, but not IL-25- or IL-17F-deficient mice, were resistant to LPS-induced endotoxin shock, as compared with wild-type mice. Nevertheless, studies using IL-6-deficient, IL-21Rα-deficient and Rag-2-deficient mice, revealed that neither IL-6 and IL-21, both of which are important for Th17 cell differentiation, nor Th17 cells were essential for the development of LPS-induced endotoxin shock, suggesting that IL-17A-producing cells other than Th17 cells were important in the setting. In this connection, IL-17A was produced by macrophages, DCs and eosinophils after LPS injection. Taken together, these findings indicate that IL-17A, but not IL-17F or IL-25, is crucial for LPS-induced endotoxin shock. In addition, macrophages, DCs and eosinophils, but not Th17 cells or γδ T cells, may be sources of IL-17A during LPS-induced endotoxin shock.     

Effect of exposure to interleukin-21 at various time points on human natural killer cell culture

Background aimsInterleukin-21 (IL-21) can enhance the effector function of natural killer (NK) cells but also limits their proliferation when continuously combined with IL-2/IL-15. Paradoxically, membrane-bound (mb)-IL-21 has been shown to improve human NK cell proliferation when cultured with IL-2/mb-IL-15. To clarify the role of IL-21, we investigated the effect of the timing of IL-21 addition to NK cell culture.MethodsIL-2/IL-15–activated NK cells were additionally treated with IL-21 according to the following schedules; (i) control (without IL-21); (ii) first week (day 0 to day 7); (iii) intermittent (the first 3 days of each week for 7 weeks); (iv) after 1 week (day 8 to day 14); and (v) continuous (day 0 to day 49). The expression of NK receptors, granzyme B, perforin, CD107a, interferon-γ, telomere length and NK cell death were measured by flow cytometry.ResultsCompared with the control (2004.2-fold; n = 10 healthy donors) and intermittent groups (2063.9-fold), a strong proliferative response of the NK cells on day 42 was identified in the “first week” group (3743.8-fold) (P < 0.05). NK cells treated with IL-21 in the “first week” group showed cytotoxicity similar to that in control cells. On day 28, there was a significant increase in cytotoxicity of “first week” NK cells that received IL-21 treatment for an additional 2 days compared with the “first week” NK cells (P < 0.05).ConclusionsThese data suggest that controlling temporal exposure of IL-21 during NK cell proliferation can be a critical consideration to improve the yields and cytotoxicity of NK cells.     

Suppression of IL-2-induced SAA gene expression in mice by the administration of an IL-1 receptor antagonist

The hepatic acute phase response induced by the administration of interleukin (IL)-2 is most likely mediated by secondary cytokines. In this investigation, we examined the role of endogenous IL-1 in the synthesis of the hepatic acute phase protein serum amyloid A (SAA) during IL-2 treatment. The injection of IL-2 induced SAA gene expression in the liver. The concurrent administration of an IL-1 receptor antagonist (IL-1RA) markedly reduced hepatic SAA mRNA levels and, to a lesser extent, SAA protein levels in the serum. Although IL-1 is an inducer of IL-6 production, the administration of the IL-1RA had no effect on circulating IL-6 levels in IL-2-treated mice. These findings suggest that the production of IL-1 is an important factor in the induction of SAA mRNA in mice undergoing immunotherapy with IL-2.     

Large intra-individual variability of plasma cytokines in healthy young men: a two 24-h study over a month

Cytokine levels in blood are not yet fully considered as biomarkers for disease even if some significant progresses have been made in linking certain cytokines to some diseases. The aim of this study was to look for the stability of some cytokines in blood collected in two different days separated by one month. Fifteen healthy young men aged 20–30 years were selected for this study. Each subject participated in two 24-h sessions spaced a month apart. Blood sample was taken at 11:00, 17:00, 22:00, 01:00, 04:00, 06:00, and 08:00. Concentrations of interleukin-6, interleukin-1-receptor antagonist, soluble IL-2 receptor, interleukin-1 beta, and interleukin-2 were measured in serum. The circadian pattern of each variable was compared between the two days. The results show that there is no reliability for the measured cytokines. This study shows that cytokine levels measured in blood are neither reliable variables nor considered as stable markers in healthy subjects.     

The involvement of IL-6 and IL-8 in acute invasive gastroenteritis of children

The involvement of the proinflammatory cytokines, interleukin 8 (IL-8) and 6 (IL-6), was studied during the first 72 h of acute invasive gastroenteritis. Study population included 33 infants and young children aged six months to six years and seven age-matched controls. As a group, patients with acute invasive gastroenteritis had an increased serum level of IL-8 and IL-6 as compared with healthy controls (p < 0.002 and p < 0.001, respectively). Subjects were then divided into two groups based on stool cultures (proven and non-proven bacterial cultures). Patients with bacterial-proven acute invasive gastroenteritis tended to have increased IL-8 serum concentrations (p < 0.07) as compared with those with non-proven bacterial etiologies and IL-6 levels were only detected in subjects with positive bacterial cultures (p < 0.05). When dividing each sub-group into early and late blood drawing with respect to disease onset, no statistical differences were found in each group but subjects with bacterial-proven etiologies had significant higher IL-6 levels as compared with non-proven etiologies at the two time points (p < 0.019 and p < 0.015, respectively).In conclusion, the proinflammatory cytokines, IL-6 and IL-8, are involved in acute invasive gastroenteritis. The difference in IL-6, and to a lesser degree IL-8, between proven and non-proven bacterial etiologies, needs further investigation.