L-精氨酸对体外循环后细胞因子的影响

目的　探讨 L-精氨酸 (L- arginine)对体外循环 (CPB)缺血 -再灌注损伤后全身炎症反应的抑制作用。方法　术前将 5 1例拟行心瓣膜置换术的风湿性心脏病患者随机分成两组 :L-精氨酸组 (n=2 5 ) ,术中给予 30 0 mg/kgL -精氨酸治疗 ;对照组 (n=2 6 ) ,术中给予等量的 5 %葡萄糖注射液。分别于术前、CPB后 2 h、4 h、8h、2 4 h和 4 8h采取动脉血 ,用酶联免疫吸附法分别测定血浆肿瘤坏死因子 - α(TNF- α)、白细胞介素 - 1β(IL- 1β)、白细胞介素 - 10 (IL- 10 )的浓度。　结果　两组 TNF-α、IL - 1β和 IL - 10水平于 CPB后均升高 (P<0 .0 5 ) ,TNF-α和 IL - 1β于 CPB后 4 8h恢复至基础值 ;L-精氨酸组 CPB后 4 h、8h、2 4 h TNF- α和 IL- 1β升高幅度明显低于对照组 (P<0 .0 5 ) ;IL- 10水平各时点组间比较差别无统计学意义 (P>0 .0 5 )。　结论　L-精氨酸可以降低 CPB后 TNF- α、IL- 1β的血浆水平 ,具有抑制 CPB缺血 -再灌注损伤后全身炎症反应的作用。     

严重烧伤患者早期几种细胞因子的变化意义

目的　观察细胞间粘附分子 1、白细胞介素 10及肿瘤坏死因子α在烧伤后并发症中的变化。方法　采用ELISA法检测严重烧伤早期 ,19例患者不同时相点外周血 3种细胞因子的水平及其变化 ,另选 11名健康志愿者为对照。　结果　 3种细胞因子的含量在伤后明显升高 ,合并有低血容量休克、脓毒血症或多器官功能障碍综合征 (MODS)时 ,升高更加明显 (P <0 .0 5～ 0 .0 1)。结论烧伤后早期动态监测 3种细胞因子的变化 ,对脓毒症及MODS的发生、发展具有一定预警意义     

己酮可可碱对大鼠内毒素性急性肺损伤炎症反应的影响

目的探讨己酮可可碱对大鼠内毒素(LPS)诱导急性肺损伤(ALI)炎症反应的影响。方法腹腔注射0.01%LPS1mg/kg,16h后在机械通气下气管内滴注1.5mg/kg(0.5ml)LPS建立大鼠内毒素性ALI模型。24只大鼠随机分为生理盐水对照组(C组)、急性肺损伤组(LPS组)和己酮可可碱组(PTX组),每组8只。7h后处死大鼠。酶联免疫吸附法(ELISA)测定支气管肺泡灌洗液(BAL)中肿瘤坏死因子α(TNF-α)、白细胞介素-10(IL-10)的含量,测肺湿/干重比,并观察BAL白蛋白浓度。结果与LPS组相比,PTX组大鼠BAL中TNF-α浓度、肺湿/干重比以及BAL白蛋白浓度显著降低(P<0.05),而IL-10显著升高。结论己酮可可碱能显著抑制内毒素性急性肺损伤大鼠的炎症反应,具有一定的肺保护作用。     

丙泊酚对内毒素性急性肺损伤大鼠血清TNF-α、IL-1β及IL-10的影响

目的探讨内毒素性急性肺损伤(ALI)大鼠用丙泊酚后处理对血清肿瘤坏死因子(TNF)-α、白细胞介素(IL)-1β和IL-10影响。方法雄性SD大鼠96只,随机均分为四组,每组24只。脂多糖(LPS)致伤组(B组)、丙泊酚低剂量治疗组(C组)和丙泊酚高剂量治疗组(D组)经尾静脉注射LPS 5 mg/kg制作ALI模型;之后生理盐水对照组(A组)和B组泵入生理盐水,C、D组分别注射丙泊酚2、4 mg/kg后再分别泵入4、8 mg.kg-1.h-1。分别在制模后1、2、3、4 h抽取动脉血测定TNF-α、IL-1β及IL-10的水平。结果制模后各时点A组大鼠TNF-α、IL-1β和IL-10含量均明显低于其它三组(P<0.05或P<0.01)。制模后1、2 h B组TNF-α、IL-1β和IL-10含量明显高于C、D组(P<0.01),C组IL-1β和IL-10含量明显高于D组(P<0.05或P<0.01)。制模后3、4 h B组IL-1β和IL-10含量仍明显高于C、D组(P<0.01),C组显著高于D组(P<0.01)。结论丙泊酚可以显著抑制ALI大鼠血清TNF-α、IL-1β及IL-10上升的程度。     

抗细胞因子治疗脓毒症临床试验的生理学基础

本文介绍了应用ＴＮＦ－α抗体，ＴＮＦ－α受体，ＩＬ－１受体拮抗物和ＩＬ－１受体治疗实验性和临床脓毒症的效应。     

不同剂量血液滤过对内毒素休克猪生存时间和细胞因子水平的影响

目的 探讨不同剂量连续性血液滤过（CVVH）对细胞因子的清除作用以及对血浆细胞因子水平的影响。 方法 采用静脉注射内毒素（E.coli O111: B4,15.7 μg/kg）的方法诱导内毒素休克猪模型。将内毒素休克猪按随机数字表法分为对照组(n=6)、 CVVH组 (n=6,前稀释法,等于后稀释法的45 ml·kg-1·h-1）和高容量血液滤过（HVHF）组 (n=6,前稀释法,等于后稀释法的70 ml·kg-1·h-1）。于造模前（基线）、成模时（T0）,成模后1 h（T1）、6 h（T6）、12 h（T12）、24 h（T24）分别测定血浆肿瘤坏死因子α（TNF-α）、白细胞介素（IL）6、IL-10和IL-18水平。 结果 对照组动物平均生存时间为（15.4±5.2） h;CVVH 组为(21.4±7.1) h;HVHF组为（22.4±6.7） h,CVVH组和HVHF组的生存时间显著高于对照组（均P < 0.05）。3组动物的心率（HR）、平均动脉压（MAP）、中心静脉压（CVP）和心排出量（CO）之间差异无统计学意义（P > 0.05）。内毒素休克猪成模后出现BUN和Scr的进行性升高,两治疗组的BUN和Scr水平显著低于对照组（P < 0.05）,但两者之间差异无统计学意义（P > 0.05）。对照组TNF-α和IL-6水平在T1时达高峰,IL-10水平在T0时最高,随后不断下降。IL-18水平在成模后上升,后无明显变化。CVVH组血浆IL-10（T6、T12、T24）水平低于对照组（P < 0.05）。HVHF组TNF-α（T6）和IL-10（T6、T12、T24）水平低于对照组和CVVH组（P < 0.05）,3组的IL-6和IL-18水平差异无统计学意义,IL-6（T6、T12）水平和动物生存时间呈负相关（P < 0.05）。 结论 CVVH和HVHF治疗均能显著延长内毒素休克猪的生存时间。CVVH能有效清除IL-10;HVHF治疗能清除TNF-α和IL-10;但CVVH和HVHF对IL-6和IL-18水平无明显影响;CVVH和HVHF均能有效清除BUN和Scr。IL-6水平是预测内毒素休克预后的独立指标。     

胆碱能递质对LPS刺激外周血释放细胞因子的影响

目的观察拟胆碱药物对LPS刺激正常人全血细胞释放TNFα,IL-6和IL-10的影响,评价胆碱能递质在全血中抗炎的综合效应.方法在LPS刺激的全血中分别加入不同浓度的乙酰胆碱和氯化氨甲酰胆碱孵育5h;用ELISA方法测定培养细胞上清液中TNFα,IL-6和IL-10的浓度.结果乙酰胆碱和氯化氨甲酰胆碱对LPS刺激外周血释放TNF和IL-6均有抑制作用,并呈现一定的剂量依赖关系,但氯化氨甲酰胆碱的抑制作用强于乙酰胆碱.IL-10也呈现类似的规律.结论胆碱能递质不仅抑制LPS刺激的外周血释放炎症性细胞因子,在一定程度上也影响抗炎因子的释放,提示其具有免疫调节作用.     

吸入NO对婴幼儿体外循环中细胞因子变化的影响及意义

目的 探讨吸入一氧化氮(NO)对婴幼儿体外循环手术中细胞因子变化的影响及意义.方法 室间隔缺损的婴幼儿30例随机分为对照组和NO组,NO组在体外循环期间吸人40×10-6NO直至关胸.在体外循环前、主动脉开放后1、3、5、10 min分别取右上肺静脉血和右心房血测定TNF-α、IL-8、IL-10.结果 NO组IL-10水平较对照组增高(P<0.01),TNF-α、IL-8则较对照组明显降低(P<0.05).结论 NO能抑制炎症性细胞因子,促进抗炎细胞因子的活性,故可减轻体外循环并发症.     

重楼总皂苷对多发骨折-脂多糖两次打击模型大鼠血清细胞因子水平的影响

目的：探讨重楼总皂苷（RPTS）对多发骨折-脂多糖两次打击模型大鼠血清TNF-α、IL-1β及IL-6水平的影响。方法：68只Wistar大鼠随机分成5组,除空白对照组外,其余各组按多发骨折-脂多糖两次打击模型标准制模。制模成功后1h,除空白对照组和模型对照组外各组予以不同浓度的RPTS灌胃,干预后6h采血,以ELISA法检测血清中TNF-α、IL-1β及IL-6浓度。结果：大鼠血清TNF-α、IL-1β及IL-6浓度,模型对照组与空白对照组相比较明显升高（P〈0.001）,而RPTS各干预组与模型对照组相比较却明显下降（P〈0.001）,差异均有统计学意义。结论：重楼总皂苷可以降低多发骨折-脂多糖两次打击模型大鼠血清中的TNF-α、IL-1β及IL-6水平。     

细胞因子对精子发生及其功能的影响

细胞因子是细胞与细胞间相互沟通的信号分子,细胞因子之间彼此诱生,相互协同或拮抗作用介导并维持细胞间的协调关系。男性精浆中白细胞介素(IL)-2、IL-6、肿瘤坏死因子(TNF)-α等细胞因子对男性生殖有一定的影响。     

Impact of monocytic cytokines in polytrauma patients with orthopedics injures

ObjectiveOrthopedic injuries are a growing epidemic affecting predominantly, the young population, after trauma. Polytrauma patients with a femoral fracture and with Injury Severity Score of >15 are of special concern because of complications like Systemic inflammatory response syndrome (SIRS), Multi-organ dysfunction syndrome (MODS) and sepsis. Against this background. We aimed to assess the role of monocytic cytokines in the development of complications in patients, having isolated diapheseal fracture of femur as compared to those having diapheseal fracture of femur along with ISS score >15.MethodologyPatients were divided into to two groups: in first group, only those patients who had isolated femur fracture were included (named as ‘Group A’). In the second groups patients having femur fracture along with ISS >15 at the time of admission (named as ‘Group B’), were included. The study used flowcytometry based intracellular cytokine assay to circumvent the problem associated with extracellular cytokine assay.Results and ConclusionA total of 20 patients aged between 20 and 55 years, presenting to the emergency department within 24 h of injury were enrolled in Group ‘A’ and ‘B’ as per criteria mentioned above. Intracellular expression of cytokines in isolated femur fracture tends to normalize towards healthy control in the late phase of trauma. Elevated levels of IL-8 and IL-6 levels in late phase (Day 10) of trauma. IL-8 and IL-6 may increases to compensate the higher levels of IL-1β. The effect of cytokines on the severity of injury was observed. This complex action of immune cells and proinflammatory cytokines were seen in initial and later stage of trauma.     

早期生长反应基因-1与急性胰腺炎大鼠肝损害的关系

目的 通过观察早期生长反应基因-1在大鼠不同程度AP及AP发病后不同时间肝组织的表达,及检测血清炎性细胞因子与肝实质酶水平,研究早期生长反应基因-1与AP肝脏损害的关系.方法 先将24只雄性Wistar大鼠随机均分为4组,即A、B、C、D组,分别于胆总管内逆行注入生理盐水或不同浓度牛磺胆酸钠溶液,3h后处死动物,留取血清、肝脏组织.另将30只雄性Wistar大鼠随机均分为5组,即E、F、G、H、I组,5%牛磺胆酸钠溶液胆管内逆行注射后1h、3h、6h、12h、24h处死动物同上留取标本.检测血清AST、LDH、TNF-a、IL-113水平,并对肝组织进行EGR-1免疫组化染色.结果 (1)A、B、C、D四组动物炎性细胞因子TNF-a、IL-1β,肝实质酶AST及LDH水平均随着牛磺胆酸钠浓度的升高而逐渐上升;(2)肝组织进行EGR-1免疫组化染色显示,在不同程度AP组,EGR-1表达量随AP病情程度加重而逐渐增加,并与反映AP病情指标如肝实质酶、炎性细胞因子水平均呈显著正相关,且表达部位也有所不同.EGR-1在AP发病后不同时间肝组织的表达,具有极明显的细胞种类与部位的差异.结论 EGR-1可能与AP时伴发的肝脏损害有关,其机制可能与其介导炎性细胞因子生成有关.     

Local expression of tumor necrosis factor-alpha and interleukin-10 on wound healing of intestinal anastomosis during endotoxemia in mice

BACKGROUND: This study aimed to evaluate the integrity of anastomotic wound healing after digestive surgery under septic conditions and define the participation of local expression of tumor necrosis factor-alpha (TNF-alpha) and interleukin-10 (IL-10) around the anastomotic segment. MATERIALS AND METHODS: Experimental animals were divided into lipopolysaccharide (LPS) and control groups, which had either LPS or normal saline solution injected into the peritoneal cavity 24 h before transection and anastomosis of the colon. Anastomotic bursting pressure (ABP) and tissue hydroxyproline concentration (HP) were measured as indicators of wound healing. Immunohistochemical staining for TNF-alpha and IL-10 on tissue samples obtained from the anastomotic segment were examined 1, 6, and 24 h after the operation. The reactive cells were counted under light microscopy. RESULTS: ABP and HP were significantly lower in the LPS group than in the control group 7 days after surgery. In the LPS group, TNF-alpha expression increased about threefold over that in the control group 1 h after the operation. TNF-alpha-reactive cells were observed until 24 h after the operation in the LPS group, but not in the control group. On the other hand, IL-10 was not expressed in the control group during the observed period, whereas IL-10 was observed 24 h after the operation in the LPS group. CONCLUSIONS: It is suggested that anastomotic wound healing was impaired after the digestive surgery in animals treated with intraperitoneal LPS, and that local expression of TNF-alpha and IL-10 at the anastomotic site acts as an inhibitory factor in the wound healing process.     

CD16 inhibition increases host survival in a murine model of severe sepsis

Background

To investigate the therapeutic effect of monoclonal antibody (mAb)–induced CD16 (FcγRIII) inhibition in a murine model of high-grade (severe) sepsis.

Materials and methods

In a prospective controlled animal study, 2 μg of CD16/32 (FcγRIII/FcγRII) or the same volume of normal saline was administered intraperitoneally to BALB/c FcγRII^−/− mice at the time of cecal ligation and puncture (CLP) in a murine model of high-grade sepsis. Subcutaneous administration of CD16/32 (0.5 μg/24 h) or normal saline continued for 7 d. Survival was evaluated, and the underlying therapeutic mechanism of mAb-induced CD16 inhibition was investigated.

Results

CD16 expression was significantly increased on peripheral blood CD14⁺ monocytes from mice with high-grade sepsis compared with non–septic control mice (1579.40 ± 217.75 versus 461.10 ± 36.13; P < 0.05). CD16/32 mAb treatment increased the survival of mice with high-grade sepsis (P < 0.05) and significantly decreased their elevated levels of serum tumor necrosis factor α (36.70 ± 9.97 versus 52.60 ± 10.69; P < 0.05) and interleukin 1β (1149.40 ± 244.09 versus 2605.60 ± 353.74; P < 0.05) at 6 and 24 h after CLP, respectively. Moreover, CD16/32 mAb-treated mice with high-grade sepsis had fewer bacteria in their blood and peritoneal lavage than mice just treated with normal saline at 24 h after CLP (P < 0.05).

Conclusions

CD16/32 mAb-induced CD16 inhibition increased the survival of mice with high-grade sepsis, which may have been because of the concomitant suppression of tumor necrosis factor α and interleukin 1β as well as the enhancement of monocyte phagocytosis. Thus, targeted inhibition of CD16 can potentially improve the outcome of selected patients with severe sepsis.     

Elevated inflammatory cytokine expression in CSF from patients with symptomatic thoracic disc herniation correlates with increased pain scores

BACKGROUND

The pathophysiology of pain in patients with symptomatic thoracic disc herniation (TDH) remains poorly understood. Mere mechanical compression of the spinal cord and/or the exiting nerve root by a prolapsed disc cannot explain the pathogenesis of pain in all cases. Previous studies report a direct correlation between the levels of proinflammatory cytokines in disc biopsies and the severity of leg pain in patients with lumbar disc herniation. A similar correlation in patients with TDH has not been investigated.

钌红对严重烧伤早期心肌能量代谢的影响

目的 探讨钌红对严重烧伤早期心肌能量代谢的影响。方法 Wistar大鼠24只,随机分为正常对照组、烧伤组和烧伤钌红治疗组。烧伤组、烧伤钌红治疗组大鼠造成30％总体表面Ⅲ度烧伤,伤后30min经腹腔补液,烧伤治疗组同时于颈外静脉推注钌红(2mg/kg体重）,3h后再推注1次。伤组和烧伤治疗组动物于伤后6h活杀。测定心肌线粒体呼吸功能、Ca^2 浓度（[Ca^2 ]m)及心肌组织ATP、ADP、AMP和乳酸含量。结果 钌红治疗组[Ca^2 ]m较烧伤组显著降低,线粒体呼吸控制率（RCR）、Ⅲ态呼吸速率（ST3）明显升高,Ⅳ态呼吸速率（ST4）降低;钌红治疗组ATP含量较烧伤组升高100.4%,同时ADP、AMP含量明显低于烧伤组,且钌红治疗组乳酸仿较烧伤组降低53.5%。结论 钌红治疗可改善严重烧伤早期线粒体功能和心肌能量代谢。     

脂联素对脓毒症大鼠早、晚期炎症介质表达的影响

目的 研究脂联素(adiponectin,APN)对内毒素(lipopolysaccharide,LPS)诱导的脓毒症大鼠早、晚期炎症介质表达的影响.方法 将96只健康雄性Wistar大鼠按随机数字表法分为4组(每组24只):对照组(C组)、模型组(LPS组)、APN预处理组(APN+LPS组)及APN后处理组(LPS...     

TAKEDA-143242 increased survival via reduced cytokines in porcine peritonitis

TAKEDA-143242 (TAK-242) is a small molecule shown to inhibit lipopolysaccharide-induced intracellular signaling and inflammation. In vitro studies demonstrated that TAK-242 can prevent release of TNF-α, IL-1β, and IL-6 from activated macrophages of several species, including pigs. This study tested the hypothesis that TAK-242 would protect pigs from lethal gram-negative peritonitis via an anti-cytokine mechanism. A validated model of porcine gram-negative peritonitis, which employs chronically inplantated cardiac transducers and aortic and pulmonary artery catheters, was used. Pigs were pretreated with TAK-242 or its vehicle via a blinding procedure prior to intraperitoneal implantation of an LD(90) dose of E. coli 0111:B4 in a fibrin clot. Ten pigs were treated with TAK-242 and nine with its vehicle. All ten TAK-242 treated pigs survived, while three of the nine vehicle treated pigs survived (P = 0.01 χ(2) test). Pulmonary artery pressure increased markedly in vehicle pigs, and this elevation was significantly (two-way ANOVA) obviated in TAK-242 treated group. Circulating levels of cytokines in vehicle treated pigs showed increased expression (3930 ± 1770 at 1 h, 1007 ± 400 TNF-α at 2 h; 719 ± 308 of IL-1β at 2-6 h; 33000 ± 1000 of IL-6 at 2-4 h [pg/mL, mean ± SEM]). Peak circulating levels of these cytokines were significantly reduced by pretreatment with TAK-242 (<25 pg/mL TNF-α ; <100 pg/mL IL-1β; 0-1700 pg/mL IL-6, peak values). This study found that pretreatment with TAK-242 yielded significantly positive survival benefit in a lethal sepsis model that was associated with improved cardiovascular status and suppressed cytokine release.