类风湿关节炎患者血清维生素D水平与IL-10、IL-37、IL-6和IL-17的相关性分析

目的检测不同病程类风湿关节炎(RA)患者血清中维生素D、血清抑炎细胞因子白细胞介素(IL)-10和IL-37与炎症细胞因子IL-6和IL-17水平,对维生素D与炎症相关因子相关性进行分析。方法将112例确诊为RA的患者设为观察组,根据疾病活动度评分(DAS28)分为缓解组、低度组、中度组和重度组,选取32例体检健康者作为对照组。使用化学发光法检测维生素D水平,酶联免疫吸附试验检测各组IL-10、IL-37、IL-6和IL-17水平。采集临床一般资料进行相关性分析。结果观察组血清中维生素D水平明显低于对照组,随着病情加重,维生素D水平逐渐下降,且各组间差异有统计学意义(P0.05)。观察组4种细胞因子水平均明显高于对照组,差异有统计学意义(P0.05);随病情加重,4种细胞因子呈上升趋势,各组间比较差异有统计学意义(P0.05),但IL-10水平差异无统计学意义(P0.05),缓解组IL-37、IL-6和IL-17水平均明显高于对照组,差异有统计学意义(P0.05)。对照组血清维生素D水平与抑炎细胞因子IL-10和IL-37及炎性细胞因子IL-6和IL-17水平之间不相关(P0.05),观察组各组维生素D水平与IL-10水平不相关(P0.05),缓解组维生素D水平与IL-10、IL-37、IL-6和IL-17水平之间不相关(P0.05);低度组、中度组和重度组维生素D水平与IL-37、IL-6和IL-17水平之间均呈负相关(r=-0.616 5～-0.347 2,P0.05)。结论维生素D与不同病程RA患者血清中抑炎细胞因子IL-10和IL-37与炎症细胞因子IL-6和IL-17水平存在相关性,提示维生素D参与调节炎症相关细胞因子水平,影响RA的进程,检测其表达水平对RA的病情变化具有重要的临床意义。     

环磷酰胺对小鼠急性百草枯中毒细胞因子的影响

目的:探讨环磷酰胺处理后对小鼠急性百草枯中毒细胞因子的影响。方法:100只小鼠,雌雄各半,随机分为4组,分别为生理盐水组(N组)、百草枯对照组(P组)、环磷酰胺对照组(C组)及环磷酰胺干预组(T组),N组给予生理盐水×2d,P组给予百草枯20 mg/kg染毒1次,第2天给予生理盐水,C组给予环磷酰胺80mg/kg×2d,T组先给予百草枯20mg/kg染毒1次,2h后给予环磷酰胺80mg/kg×2d,给药方式均为腹腔注射。给药后第1、3、5天检测小鼠肺组织中髓过氧化物酶(MPO)的含量,及血清中的TNF-α及IL-6的含量。组间及组内比较采取单因素方差分析。结果:百草枯染毒后肺组织MPO的含量短期内显著升高,第3天时开始逐渐下降;T组小鼠MPO第1天即开始显著下降,第3、5天时显著低于中毒组,但仍高于正常;百草枯染毒后小鼠血清IL-6及TNF-α含量很快达峰值,随后逐渐下降;T组小鼠血清IL-6及TNF-α含量显著低于P组,第5天时与P组比较差异无统计学意义。结论:环磷酰胺干预可通过抑制炎性细胞因子的分泌减轻炎症反应。     

细胞因子水平与肝纤维化患者治疗和预后的相关研究

目的 探讨肝纤维化患者血清细胞因子白细胞介素6(IL-6)、白细胞介素(IL-8)、白细胞介素10(IL—10)水平与疾病预后之间的关系。方法 采用酶联免疫吸附试验(ELISA)法测定肝纤维化患者治疗前后的细胞因子水平。结果 60例肝功能减退的肝纤维化患者外周血清IL-6、IL-8水平较正常对照组显著升高，IL-10水平则较正常对照组显著降低。采用口服氧化苦参碱治疗3个月后肝功能减退组IL-6、IL-8水平较治疗前降低，IL—10水平升高，但差异无显著性；3个月后肝功能恢复组的IL-6、IL-8水平较治疗前显著降低，IL—10水平则显著升高。结论 细胞因子水平与肝纤维化患者预后有关，其血清水平可作为判断肝纤维化患者预后的指标之一，氧化苦参碱可能具有一定的抗肝纤维化作用。     

高位硬膜外阻滞术治疗扩张型心肌病患者相关白细胞介素水平的变化

目的探讨高位硬膜外阻滞术(TEB)治疗前后扩张型心肌病(DCM)患者白细胞介素6(IL-6)、可溶性白细胞介素2受体(sIL-2R)和白细胞介素10(IL-10)的变化。方法TEB治疗组22例、常规治疗组13例，用ELISA方法测血清IL-6、sIL-2R和IL-10水平，比较TEB组和常规治疗组治疗前后IL-6、sIL-2R及IL-10水平的变化。结果TEB组治疗后血清IL-6和sIL-2R水平明显降低(P=0．0062，P=0．0266)，而IL-10水平有明显升高(P=0．0043)。结论TEB治疗对细胞因子有良好的调节作用，并且通过此免疫调节参与治疗扩张型心肌病。     

维生素E对高脂血症小鼠Th1和Th2细胞因子表达的影响

目的观察维生素E对高脂血症小鼠辅助性T淋巴细胞1(Th1)和辅助性T淋巴细胞2(Th2)细胞因子表达的影响。方法将50只ICR雄性性成熟小鼠随机分为A、B、C、D、E 5组,每组10只,分别给予高脂饲料、不同浓度维生素E(每日10 mg/kg、20 mg/kg、40 mg/kg)加高脂饲料及普通饲料连续喂养4周,后处死小鼠抽取静脉血观察比较血清Th1和Th2细胞因子表达情况[肿瘤坏死因子-α(TNF-α)、白细胞介素-12(IL-12)及白细胞介素-4(IL-4)、白细胞介素-5(IL-5)]及甘油三酯(TG)、胆固醇(TC)浓度。结果 A组血清TNF-α、IL-12及TG、TC浓度均高于B、C、D、E组,血清IL-4及IL-5浓度均低于B、C、D、E组,差异均有统计学意义(P0.05)。B、C、D 3组血清TNF-α、IL-12及TG、TC浓度均随维生素E剂量增加逐渐降低,血清IL-4及IL-5浓度随维生素E剂量增加逐渐升高,且3组间比较差异均有统计学意义(P0.05)。E组血清TNF-α、IL-12及TG浓度均低于B、C、D组,血清TC浓度低于B、C组,血清IL-4及IL-5浓度均高于B、C、D组,除D、E 2组血清IL-4比较差异无统计学意义外(P0.05),余差异均有统计学意义(P0.05)。血清IL-5浓度与IL-12浓度呈负相关关系。结论维生素E能抑制高脂血症所导致的免疫损伤与炎性反应,并可降低血脂。     

机械通气辅以盐酸氨溴索对老年急性呼吸窘迫综合征患者动脉血气和细胞因子的影响

目的 探讨机械通气辅以盐酸氨溴索(沐舒坦)对老年急性呼吸窘迫综合征(ARDS)患者动脉血气和细胞因子的影响.方法 对56例老年ARDS患者进入ICU后给予抗炎、吸痰、脱水和营养支持治疗,随机分为两组,治疗组在机械通气等常规治疗的基础上给予盐酸氨溴索20 mg/kg+生理盐水250 mL缓慢(3 h)静脉滴注;对照组在机械通气的基础上给予生理盐水250 mL缓慢(3 h)静脉滴注,两组连用7 d观察各项指标.比较两组患者治疗前和治疗后7 d氧合指标(PaO2/FiO2)及血清TNF-α、IL-6及IL-10浓度的变化和差异.结果 治疗后7 d,治疗组动脉血氧分压(PaO2)、动脉血氧饱和度(SaO2)、PaO2/FiO2和血清IL-10浓度明显下降(P<0.05),心率(HR)和血清TNF-α、IL-6浓度明显下降(P<0.05),与对照组比较,差异均有统计学意义(P<0.05);治疗组动脉血二氧化碳分压(PaCO2)和平均动脉压(MAP)与对照组比较,差异无统计学意义(P>0.05).结论 机械通气辅以盐酸氨溴索治疗可以改善老年ARDS患者的氧合,有效调节细胞因子的生成,提高疗效.     

HBV相关肝衰竭患者Th1/Th2型细胞因子变化及与预后的关系

目的 探讨Th1/Th2型细胞因子在乙型肝炎病毒(HBV)相关慢加急性肝衰竭(HBV-ACLF)患者中的表达变化及与预后的相关性。方法 回顾性分析2021年1月至2021年12月HBV-ACLF患者69例与慢性乙型肝炎(CHB)患者70例的临床资料，并选择同期体检的70例健康人员为对照组，比较3组对象血清Th1/Th2型细胞因子表达，并比较HBV-ACLF组不同病情程度及预后患者血清Th1/Th2型细胞因子表达水平差异。结果 HBV-ACLF组患者血清IL-2、INF-、TNF-α、IL-6高于对照组及CHB组，IL-4、IL-10低于对照组及CHB组(P<0.05);随着病情的加重，INF-、IL-6水平升高(P<0.05),IL-4、IL-10水平下降(P<0.05);生存组INF-、IL-6、TNF-α水平低于死亡组，IL-4、IL-10水平高于死亡组；血清INF-、TNF-α、IL-4、IL-6、IL-10水平是影响HBV-ACLF患者预后的独立危险因素(P<0.05)。结论 血清INF-γ、TNF-α、IL-6水平在HBV-ACLF中呈升高状态，IL-...     

乌司他丁对重度急性有机磷农药中毒患者细胞因子影响的研究

目的探讨乌司他丁干预对重度急性有机磷农药中毒（AOPP）引发多器官功能障碍综合征（MODS）患者血清TNFα、IL-6及IL-10水平动态变化的影响。方法重度AOPP引发MODS患者46例，临床随机分为常规治疗组（n=24）、乌司他丁干预组（n=22），同步检测两组患者血清中上述细胞因子的动态变化，并与健康对照组（n=20）进行对比分析。结果常规治疗组与乌司他丁干预组患者血清中TNF-α、IL-6及IL-10水平均高于健康对照组（P〈0．01）；两组治疗前后比较，血清TNF—α、IL-6及IL-10水平均有明显降低（P〈0．01），但乌司他丁干预组血清TNF-α、IL-6的降低水平较常规治疗组更明显（P〈0．01），而治疗后血清IL-10水平两组比较无显著性差异（P〉0．05）。乌司他丁干预组的病死率明显低于常规治疗组（P〈0．05），痊愈患者的住院时间也明显缩短（P〈0．01）。结论TNF-α、IL-6及IL-10等细胞因子参与重度AOPP引发MODS患者的病理过程；乌司他丁干预能明显降低重度AOPP患者血清TNF-α、IL-6水平，从而降低并发MODS的重度AOPP患者的病死率。     

乌司他丁辅助治疗对脓毒症患者炎症细胞亚群及分泌细胞因子的影响

目的:观察脓毒症患者外周血炎症细胞和细胞因子的变化,并观察乌司他丁辅助治疗对脓毒症患者炎症细胞和细胞因子表达的影响。方法:选择2014-09-2016-10入住我院重症医学科的脓毒症患者53例,分为常规治疗组(29例,给予常规集束化治疗)和乌司他丁治疗组(24例,在常规治疗基础上给予乌司他丁30万IU/次静脉注射,3次/d),于治疗前和治疗7d后采集外周血,并选择15例年龄和性别比例相匹配的健康志愿者作为对照组,检测辅助性T细胞(CD3+CD4+)、杀伤性T细胞(CD3+CD8+)、自然杀伤细胞(NK细胞,CD3-CD56+)以及12种细胞因子的水平,观察乌司他丁的干预作用。结果:辅助性T细胞和杀伤性T细胞水平在脓毒症组和对照组之间差异无统计学意义,而脓毒症组中NK细胞的水平较对照组明显升高[(11.33±5.15)%vs.(11.33±5.15)%,P=0.040]。血清中IL-6和IL-8在脓毒症患者中的水平显著高于对照组(P<0.05),而IL-10水平在脓毒症患者血清中显著降低(P<0.05),余细胞因子未检出或在两组间表达差异无统计学意义。治疗前NK细胞的比例,IL-6、IL-8以及IL-10的水平在常规治疗组和乌司他丁治疗组之间差异无统计学意义,乌司他丁治疗辅助治疗后IL-6和IL-8的水平较常规治疗组显著下降(P<0.05),而治疗后IL-10在常规治疗组和乌司他丁治疗组比较差异无统计学意义。结论:乌司他丁治疗可有效降低脓毒症患者NK细胞水平,下调IL-6和IL-8异常升高表达,在脓毒症治疗中发挥免疫调控作用,有望改善脓毒症患者的预后。     

25-羟维生素D3水平与ITP患儿外周血T淋巴细胞相关细胞因子水平的关系

目的 探讨血清25-羟维生素D3[25(OH)D3]水平与特发性血小板减少性紫癜(ITP)患儿外周血T淋巴细胞相关细胞因子水平的关系.方法 将2017年8月至2019年9月于该院就诊的ITP患儿共127例纳入研究作为患儿组.根据血清25(OH)D3水平,将127例患儿又分为缺乏组(低于30 nmol/L)、降低组(30～50 nmol/L)和正常组(高于50 nmol/L).另外,将60例于该院门诊体检的健康儿童纳入研究作为对照组.对纳入研究的儿童进行血清25(OH)D3、T淋巴细胞相关细胞因子水平[白细胞介素(IL)-2、IL-4、IL-6、IL-10、IL-17、干扰素-γ(IFN-γ)和肿瘤坏死因子-α(TNF-α)]的检测,对患儿组和对照组的上述指标水平进行比较;比较不同25(OH)D3水平ITP患儿T淋巴细胞相关细胞因子水平.观察患儿治疗4个月后的转归情况,比较治疗4个月后有效组和无效组间25(OH)D3及T淋巴细胞相关细胞因子水平.结果 患儿组25(OH)D3水平低于对照组(P<0.05),IL-2和IL-17水平高于对照组(P<0.05),IL-4和IL-10水平低于对照组(P<0.05).不同25(OH)D3水平的患儿组间IL-2、IL-4、IL-10和IL-17水平比较,差异均有统计学意义(P<0.05).治疗4个月后,有效组25(OH)D3水平高于无效组(P<0.05),有效组IL-2和IL-17水平低于无效组(P<0.05),而IL-4、IL-10的水平高于无效组(P<0.05).结论 25(OH)D3的水平可能与T细胞相关因子的表达水平密切相关,能够调节其表达水平,并可能影响ITP患儿的临床转归.     

高渗氯化钠羟乙基淀粉溶液对未控制出血性休克大鼠炎性反应的影响

目的:探讨高渗氯化钠羟乙基淀粉溶液(HHS)对未控制出血性休克(UHS)大鼠炎性反应的影响。方法:采用修订的Capone等方法制备创伤UHS模型。30只SD大鼠随机分为3组:NC组(正常对照组)、NS组(生理盐水复苏组)、HHS组(高渗氯化钠羟乙基淀粉溶液复苏组)。分别在伤后0、30、90、210min观察3组大鼠的心率;血清K+、Na+、Cl-的浓度;血浆TNF-α、IL-1β、IL-6、IL-10的浓度。结果:大鼠休克后心率显著下降,复苏后明显升高;HHS组在伤后90min时,血清Na+、Cl-浓度明显增加(P<0.05),但在伤后210min时恢复正常;两复苏组中TNF-α在休克后迅速升高,复苏后进一步上升,IL-1β与IL-6浓度在伤后90min才有明显增加,而IL-10浓度在伤后210min降低(P<0.05)。与NS组比较,HHS组在各相应时点的TNF-α、IL-1β、IL-6浓度明显下降,IL-10浓度显著增高(P<0.05)。结论:HHS有利于保持UHS大鼠血流动力学稳定,并减少促炎因子释放,促进抗炎因子合成,从而对机体产生一定的保护作用。     

Magnolol alters cytokine response after hemorrhagic shock and increases survival in subsequent intraabdominal sepsis in rats

Magnolol is a Chinese herb that has potent antioxidant effects. This study evaluated the effect of magnolol in the treatment of severe injury using a two-hit model in Sprague-Dawley rats. Hemorrhagic shock followed by resuscitation was performed. Intra-abdominal sepsis was induced by cecal ligation puncture. The rats were randomly segregated into the following three groups: group 1 (sham group) rats were sham-operated; group 2 (untreated group) rats received hemorrhagic shock and resuscitation and cecal ligation puncture 24 h later; and group 3 (treated group) rats were treated with magnolol and subjected to the same procedures as group 2. Plasma cytokine levels and tissue cytokine contents of lung, including tumor necrosis factor alpha (TNFalpha) and interleukin (IL)-10 were assayed after hemorrhagic shock and sepsis. Pulmonary injury study was performed using Evans blue dye and survival analysis was performed after development of sepsis. Plasma and tissue TNFalpha levels increased after hemorrhagic shock. Magnolol treatment blunted the TNFalpha levels in plasma and tissue. The plasma IL-10 level increased after hemorrhagic shock, whereas the tissue level of IL-10 did not change. Magnolol treatment did not alter the plasma level of IL-10 but did increase tissue level. After sepsis, TNFalpha levels in both plasma and tissue of magnolol-treated animals were significantly lower than those in untreated animals, whereas plasma and tissue IL-10 levels were not significantly different between treated and untreated groups. Pulmonary injury study showed that magnolol-treated rats had decreased pulmonary permeability after the onset of sepsis. Survival analysis showed that survival rate was significantly higher in the treated group. In conclusion, magnolol modifies the cytokine response after hemorrhagic shock and resuscitation; the proinflammatory cytokine response is suppressed. The modified cytokines response induced by magnolol may result in decreased tissue injury and increased survival in subsequent intra-abdominal sepsis.     

Comparison of the mortality and inflammatory response of two models of sepsis: lipopolysaccharide vs. cecal ligation and puncture

Sepsis remains a serious clinical problem despite intense efforts to improve survival. Experimental animal models of sepsis have responded dramatically to immunotherapy blocking the activity of cytokines. Despite these preclinical successes, human clinical trials have not demonstrated any improvement in survival. We directly compared the mortality, morbidity, and immunopathology in two models of sepsis, one due to lipopolysaccharide (LPS) and the other to cecal ligation and puncture (CLP). BALB/c mice were injected intraperitoneally with 250 microg of LPS or subjected to CLP with an 18-gauge needle. Both models yielded similar mortality (> 85%) and morbidity. Additionally, neutropenia and lymphopenia developed in both groups. Plasma and peritoneal levels of cytokines (TNF, IL-1, IL-6, and the chemokines KC and MIP-2) were measured at 1.5, 4, and 8 h after challenge. LPS induced substantially higher levels of cytokines in both compartments with peak levels between 1.5 and 4 h that began to decline at 8 h. In contrast, cytokine levels in the CLP model were continuing to increase at the 8 h-time point and often exceeded the LPS-induced values at this time. Our data demonstrate that the LPS and CLP models have similar mortality but significant differences in the kinetics and magnitude of cytokine production. Immunotherapy for sepsis based on cytokine production after LPS challenge is misdirected because the LPS model does not accurately reproduce the cytokine profile of sepsis.     

Effect of treatment with Xuebijing injection on serum inflammatory mediators and Th1/2 of spleen in rats with sepsis]

OBJECTIVE: To study the effect of treatment with Xuebijing injection on pro- or anti-inflammatory response and pathologic changes in immune organs in rats with sepsis. METHODS: Sepsis was reproduced in rats by cecal ligation and puncture. Rats were divided into four groups i.e. sham operation, sepsis, sepsis with levofloxacin treatment, and Xuebijing treatment groups. Blood samples were collected at 3, 24 and 72 hours after model was reproduced. Enzyme linked immunoadsordent assay (ELISA) was used to determine the levels of serum tumor necrosis factor-alpha (TNF-alpha) and interleukin-10 (IL-10), expression level of spleen Th1/Th2 was assessed by FACS flow cytometer, and the pathological changes in immunological organs were examined. RESULTS: The results showed that the levels of Th1/Th2 and TNF-alpha, IL-10 were elevated in early period of sepsis, but lowered in late period of sepsis. Xuebijing could decrease the level of Th1/Th2, which showed an increase at 72 hours. Xuebijing could lower the levels of TNF-alpha and IL-10, rendering a balance of pro- and anti-inflammatory response. CONCLUSION: There is a dissonance in immunological function in sepsis, showing a depression in specific immunological function, but an exaggeration in non-specific immunological function. Xuebijing can obviously ameliorate the immunological disturbance in sepsis of rat.     

Oxygen free radicals: effect on red cell deformability in sepsis

OBJECTIVE: To examine the effect of alpha-tocopherol, a free radical scavenger, on RBC deformability, mixed venous hemoglobin saturation (SvO2), arterial-venous oxygen content difference (C[a-v]O2), pHv, and survival during sepsis. DESIGN: Randomized controlled study. INTERVENTIONS: Sprague-Dawley rats were randomized to three groups: sham, cecal ligation and puncture, or alpha-tocopherol/cecal ligation and puncture (pretreatment with alpha-tocopherol before cecal ligation and puncture). MEASUREMENTS AND MAIN RESULTS: The cecal ligation and puncture group had a significantly (p less than .05) higher SvO2 and lower C (a-v)O2, pHv, and survival rate when compared with alpha-tocopherol/cecal ligation and puncture and sham groups. No difference in pHa existed between groups. CONCLUSIONS: The alpha-tocopherol treatment improves survival in sepsis. RBC deformability during sepsis is prevented by alpha-tocopherol, suggesting that free radicals may cause the decrease in RBC deformability. This study provides indirect evidence that decreased RBC deformability may play a role in the physiologic peripheral shunting and decreased microcirculatory flow that occurs during sepsis.     

依达拉奉对脑缺血大鼠内源性神经干细胞的影响

背景:依达拉奉(MCI-186)是一种新型自由基清除剂,已证实其能减轻急性脑梗死后的脑组织水肿、具有神经保护作用。目的:探讨自由基清除剂MCI-186对大鼠缺血脑组织内源性神经干细胞的作用。方法:Longa法构建SD大鼠大脑中动脉缺血2h再灌注模型,分两组在动脉阻塞后立即开始予MCI-186或磷酸盐缓冲液治疗,在术后1,3d和7d,动态测定缺血周边脑组织丙二醛的含量以及脑源性神经生长因子蛋白和mRNA的表达,以及缺血脑区域Nestin阳性细胞Caspase-3阳性细胞表达,同时进行神经功能测定。结果与结论:与假手术组相比,磷酸盐缓冲液组脑组织丙二醛水平明显升高,MCI-186治疗后明显降低(P均<0.01);磷酸盐缓冲液组缺血后1d,MCI-186组缺血后1,3d脑源性神经生长因子mRNA和蛋白的表达明显升高(P<0.01)。缺血后3d和7dMCI-186组Nestin阳性细胞明显高于磷酸盐缓冲液组(P<0.05),Caspase-3阳性细胞显著低于磷酸盐缓冲液组(P<0.05)。缺血后7dMCI-186组神经功能明显优于磷酸盐缓冲液组。结果提示,MCI-186能抑制脂质过氧化,增加缺血脑组织的脑源性神经生长因子分泌,保护神经干细胞,减少细胞凋亡。     

Antibiotic treatment in a murine model of sepsis: impact on cytokines and endotoxin release

Experimental and clinical studies in sepsis indicate that antibiotic therapy may induce the release of endotoxin (LPS) from the outer membrane of gram-negative bacteria and therefore may affect the physiologic response and survival. The aim of this study was to evaluate if antibiotics commonly used to treat secondary peritonitis are capable of changing survival rates, proinflammatory and anti-inflammatory cytokine concentrations, and the release of endotoxin in a murine model of sepsis. Sepsis was induced by cecal ligation and puncture (CLP) in Swiss mice using an 18-gauge needle. The animals received injections of saline solution or imipenem or a combination of ciprofloxacin plus clindamycin every 8 h for 3 days. Antibiotic treatment induced an increase in survival rate and decreased plasma and peritoneal fluid levels of TNF-alpha and IL-6 at 6 and 24 h after CLP as compared with saline-treated animals. Antibiotic-treated animals also showed an early (6 h) decrease and a late (24 h) increase in IL-10 concentration in the peritoneal fluid. LPS concentrations were elevated in all groups, but imipenem-treated animals showed higher levels (2.2 EU/mL) than ciprofloxacin plus clindamycin (1.3 EU/mL) and saline-treated (1.5 EU/mL) groups. We conclude that antibiotic-induced endotoxin release is not a major determinant in the inflammatory response and prognosis in murine models of sepsis.     

Antioxidant amplifies antibiotic protection in the cecal ligation and puncture model of microbial sepsis through interleukin-10 production

Preadministration of antioxidants such as pyrrolidine dithiocarbamate (PDTC) and phenyl N-tert-butyl nitrone (PBN) protects animals from lethality in sepsis models. However, the requirement of preadministration greatly diminishes the clinical significance of these studies. Although the synthetic antioxidant PBN has been shown to effectively protect rodents from lethality in endotoxemia (lipopolysaccharide [LPS] model), preliminary screening indicates that pre- or postadministration of PBN does not protect in the rat cecal ligation and puncture (CLP) model. We show in this report that in a rat CLP model, the administration of PBN (150 mg/kg, 30 min after CLP) followed by the antibiotic imipenem (IMP; 10 mg/kg, 1 h after CLP) significantly increased survival compared with other single treatment groups. Previously, we have shown that PBN's protection in a rat LPS model is mediated by the overproduction of the anti-inflammatory cytokine interleukin (IL)-10. We show in this study that the increase in survival found in the PBN + IMP-treated group was abrogated by immunoneutralization with anti-IL-10 antibody, indicating that endogenous IL-10 is an effective protective factor. Plasma LPS levels were shown to be elevated after imipenem treatment, and the increased LPS level could have assisted to overproduce endogenous IL-10, as in the case of the PBN-treated LPS model. Statistical analysis indicated that the increase of IL-10 in PBN + IMP-treated group at early time period has significant association to the improvement of survival.     

Colon ascendens stent peritonitis--a model of sepsis adopted to the rat: physiological, microcirculatory and laboratory changes

The colon ascendens stent peritonitis (CASP) procedure creates an intestinal leakage of feces, resulting in diffuse peritonitis and polymicrobial sepsis. Mouse models of CASP have been used to study sepsis experimentally. The aim of the present study was to establish CASP sepsis in rats and to provide basic functional characteristics of this model. In analogy to the mouse model, 3 degrees of severity of CASP sepsis, 2 sublethal and 1 lethal, were established depending on the stent diameter. Radio-telemetric recordings in a sublethal model showed that the nonsurvivors remained hemodynamically stable until approximately 1 h before death, when heart rate and blood pressure fell rapidly. Intestinal microcirculatory changes were analyzed 3, 6, 12, and 18 h after CASP surgery using intravital microscopy in a sublethal model. After 18 h, the numbers of the leukocytes firmly adhering to the endothelium and of the ones temporarily interacting were significantly increased. The levels of IL-6 and IL-1beta increased continuously during the CASP experiments while remaining unchanged in the sham group. TNF-alpha and IL-10 levels of CASP animals reached a maximum after 12 h. In conclusion, a rat model of CASP sepsis has been established and characterized with regard to alterations in cardiovascular and microcirculatory function as well as plasma cytokine levels. In experimental settings where genetically engineered animals are not required, it will facilitate detailed examination of dynamic changes in integrated organ function during the course of sepsis and the investigation of treatment strategies.