Effect of interleukin-8 on glomerular sulfated compounds and albuminuria

To evaluate the effect of interleukin-8 (IL8) on glomerular basement membrane (GBM) sulfated compounds and albuminuria, we infused IL8 in 1% bovine serum albumin (BSA) for 5 days into the left renal artery of Holtzman male rats at the rate of 10 μl/h using an osmotic pump. Control rats received 1% BSA. A significant increase in urinary albumin/creatinine ratio was seen on the last day of IL8 infusion (0.38±0.11, mean ± SEM) when compared with albumin/creatinine ratio prior to infusion (0.19±0.04, P = 0.04). No significant differences in urinary albumin excretion prior to and after infusion of 1% BSA were observed. On the last day of infusion, rats were injected with ³⁵sulfate (1.0 mCi/200 g body weight) intraperitoneally and killed after 8 h. Glomeruli were isolated and GBM obtained. After 5 days of IL8 administration, there was a significant increase in ³⁵sulfate uptake by GBM of the infused kidney (76±10 cpm/dry glomerular weight, mean ± SEM) compared with the uptake seen in the contralateral kidney (53±9, P = 0.05). The in vivo infusion of IL8 increased the ³⁵sulfate uptake by GBM and augmented the urinary albumin/creatinine ratio, suggesting that IL8 may induce albuminuria by altering the metabolism of the GBM sulfated compounds. This hypothesis needs to be confirmed by studies on glomerular charge selectivity and GBM anionic sites during the course of the infusion. Moreover, the persistence of the effect needs to be evaluated by prolonging the infusion for more than 5 days. Received June 3, 1996; received in revised form and accepted October 18, 1996     

The effects of maternal inflammation on neuronal development: possible mechanisms

That maternal inflammation adversely affects fetal brain development is well established. Less well understood are the mechanisms that account for neurodevelopmental disorders arising from maternal inflammation. This review seeks to begin an examination of possible sites and mechanisms of action whereby inflammatory cytokines - produced by the mother or by the fetal brain - could impact the developing fetus. We focus first on the placenta where cytokines maintain the immunological environment that prevents maternal rejection of the fetus. Following a brief examination of placental transfer of maternal cytokines, the focus turns on embryonic microglia, early and ubiquitous residents of the developing brain. Finally, a more intense examination of interleukin-6 (IL-6) and bone morphogenetic proteins (BMPs) provides examples of glial- or maternal-derived cytokines that are known to have profound effects on developing systems and that could, if dysregulated, have undesirable consequences for brain development.     

溴环己胺醇预先给药对大鼠盐酸吸入性肺损伤的作用

目的 观察溴环己胺醇预先给药对大鼠盐酸吸入性肺损伤是否具有保护作用，并探讨其可能机制。方法30只健康 SD 大鼠，随机分成3组，A 组：生理盐水吸入组；B组：稀盐酸吸入组；C组：稀盐酸吸入 溴环己胺醇处理组，每组10只。C 组腹腔注射溴环己胺醇，1次/d，连续3d，A、B 组以等体积生理盐水代替。第3天注药后30min，B、C 组气管注入pH 值为1.25的稀盐酸1.2ml/kg，制成盐酸吸入性肺损伤模型，A 组气管注入生理盐水1.2ml/kg。观察注药后5h 动脉血气、氧合指数(PaO_2/FiO_2)、肺湿/干重比(W/D)、肺组织及血清中肿瘤坏死因子-α(TNF-α)、白细胞介素-8(IL-8)水平。结果 与 A 组比较，B、C 组 PaO_2、PaO_2/FiO_2降低(P<0.01)，B、C 组W/D、B 组肺组织 TNF-α、IL-8含量、血清 IL-8浓度升高(P<0.01)。与 B 组比较，C 组 PaO_2、PaO_2/FiO_2升高(P<0.01)，C 组W/D、肺组织TNF-α、IL-8含量及血清 IL-8浓度降低(P<0.01)。结论 溴环己胺醇可能通过抑制 TNF-α、IL-8炎症因子的产生和释放机制对盐酸吸入性损伤肺产生保护作用。     

实质器官移植术后血浆IL-18、IL-10、IL-4检测在人巨细胞病毒感染中的意义

目的 探讨实质器官移植术后血浆中白介素18（IL－18）、白介素10（IL－10）、白介素4（IL－4）水平的检测在人巨细胞病毒（HCMV）感染中的意义。方法 对24例实质器官移植受者，用免疫组化法监测HCMV抗原血症。然后采用ELISA法测定血浆中IL－18、IL－10及IL－4的水平。结果 HCMV抗原阳性组IL－18的水平高于阴性组（P＜0.01），IL－10及IL－4的水平低于阴性组（均P＜0.05）。结论 血浆IL－18的水平可作为预测移植患者HCMV感染的一个有效指标，IL－10及IL－4的水平则可作为患者HCMV感染后体内免疫抑制程度的监测指标之一。     

脑胶质瘤白细胞介素-6自分泌或旁分泌环路的研究

目的　研究白细胞介素 6(IL 6) /IL 6受体 (IL 6R)自分泌或旁分泌环路与脑胶质瘤的关系。方法　采用逆转录 聚合酶链反应 (RT PCR)方法检测IL 6和IL 6R基因在 4株脑胶质瘤细胞株、62例脑胶质瘤组织标本、5例良性脑膜瘤组织和 5例人正常脑胶质细胞中的表达 ;将IL 6单抗 (McAb)或IL 6RMcAb与脑胶质瘤细胞共同孵育 ,四甲基偶氮唑蓝 (MTT)比色法检测对细胞生长的抑制作用。结果　脑胶质瘤细胞株C6、9L、U 2 5 1和SHG44均有IL 6和IL 6R的表达 ,脑胶质瘤组织标本中 47例 (75 .81% )表达IL 6、5 2例 (83 .87% )表达IL 6R、41例 (66.13 % )同时表达IL 6和IL 6R ;良性脑膜瘤组织 4例表达IL 6,人脑正常胶质细胞仅有IL 6弱表达 ,两者均无IL 6R表达。IL 6McAb和IL 6RMcAb能够显著抑制脑胶质瘤细胞的增殖 ,并存在剂量依赖关系(P <0 .0 1)。结论　脑胶质瘤很可能存在IL 6/IL 6R自分泌或旁分泌环路 ,阻断此环路可以明显抑制胶质瘤细胞的恶性增殖     

Soluble CD14 but not interleukin-6 is a new marker for clinical activity in atopic dermatitis

Summary Levels of soluble IL-2 receptors, IL-6, soluble CD23, soluble CD14 and ECP (eosinophilic cationic protein) were measured as markers of T-cell, B-cell, monocyte and eosinophilic leucocyte activation in 26 patients with atopic dermatitis (AD) on admission to (A) and at discharge from (D) the Department of Dermatology in Zurich. The serum levels of sIL-2R, IL-6, sCD23, sCD14 and ECP were significantly elevated in AD patients in comparison with the normal values of healthy donors. A significant decrease in sIL-2R (p=0.0093) and in sCD14 (p=0.0134) levels was demonstrated between A and D, correlating with the improvement in the skin intensity score (SIS). In addition, a significant correlation of the sCD14 levels and the SIS at A was demonstrated (p=0.0415). These results also incriminate monocytes in the pathogenesis of AD, indicating that, besides sIL-2R and ECP, SCD14 could also be a possible marker for the disease activity.     

硬膜外腔阻滞对胸部手术应激反应的影响

目的 观察硬膜外腔阻滞对胸部手术应激激素和细胞因子的影响。方法20例食管癌手术病人,随机分为两组,每组10例,即全麻复令硬膜外腔阻滞(GEA)组和全麻(GA)组,分别测定麻醉诱导前、手术2h、手术4h、术毕、术后1d及术后3d的血浆去甲肾上腺素、肾上腺素、血清促肾上腺皮质激素(ACTH)、皮质醇、C-反应蛋白、IL-6及IL-10的水平。结果 血浆去甲肾上腺素和血清皮质醇GEA组术中术后无显著改变,但GA组术毕和术后1d显著升高(P<0.05),术后3d恢复至术前水平,组间比较前者有显著差异(P<0.05)。两组血浆肾上腺素、IL-10术中术后均无显著变化。两组血清ACTH、IL-6及CRP术中术后均显著升高(P<0.05),组间比较无显著差异。结论 硬膜外腔阻滞可以减轻胸部手术的应激反应。IL-6是较CRP更灵敏的反映组织损伤的炎性指标。     

白细胞介素-1β对谷氨酸钠致痫大鼠海马Gs蛋白表达的影响

目的 探讨白细胞介素-1β(Interleukin-1，IL-1β)在谷氨酸钠致痫大鼠中对海马兴奋性G-蛋白α亚基(stimulated G-protein α subunit，Gsα)蛋白表达的影响，为阐明IL-1β在致痫中的作用机制提供线索。方法 免疫组织化学方法结合行为观察(SD大鼠随机分为对照组、GluNa组、IL-1β GluNa组、rhIL-1ra IL1β GluNa组和D-AP-5 IL-1β GluNa组)。结果 行为观察显示，IL-1β GluNa组大鼠痫性发作潜伏期(平均2min)较其他组(平均6min)明显缩短，且发作程度(Ⅲ～Ⅳ级)较其他组(Ⅰ～Ⅲ级)严重；对照组无痫性发作。免疫组织化学染色显示，Gsα蛋白在海马各区均有表达，IL-1β GluNa组大鼠在齿状回、CAl区和CA3区Gsa表达较其他组明显增强。结论 IL-1β参与致痫，且在谷氨酸致痫中可能通过Gs蛋白介导发挥作用。     

病毒白细胞介素-10转基因在造血干细胞中的表达

目的　观察逆转录病毒转病毒白细胞介素 10 (vIL 10 )基因在体内的表达。方法　用MSCVneo vIL 10重组体在体外转导CBA (H 2 K)小鼠的造血干细胞 (HSCs) ,给经致死照射(90 0rads)的 2 0只同基因CBA(H 2 K)小鼠注入经MSCVneo vIL 10转染的HSCs ,2× 10 6HSCs/只。酶联免疫吸附测定 (ELISA)、逆转录 聚合酶链反应 (RT PCR )、Westernblot分析vIL 10的表达。结果　移植MSCVneo vIL 10转染HSCs的 2 0只小鼠 ,移植后 8周用ELISA检测 ,其中 15只小鼠血清的vIL 10浓度为 :2 70～ 13 40ng/L ,5只小鼠血清的vIL 10为阴性。 12周后有 2只小鼠vIL 10测不出 ,13只小鼠长时间表达vIL 10达 6个月。对照组小鼠血清vIL 10均为阴性。RT PCR和Westernblot证实小鼠的器官均有vIL 10的mRNA和蛋白的表达。结论　逆转录病毒能有效地将vIL 10基因导入造血干细胞并在体内长时间表达。     

人脑胶质瘤白介素13受体基因表达与肿瘤增殖活性的关系研究

目的探讨人脑胶质瘤白介素13受体（IL-13R）基因表达与肿瘤增殖活性的关系。方法对6例正常脑组织，50例人脑胶质瘤和2个脑瘤体外细胞系采用RT—PCR法和免疫组织化学法检测IL-13R。结果人脑胶质瘤组织IL-13RαmRNA总阳性表达率70％，正常脑组织中仅1例有极弱的表达；2例恶性胶质瘤体外细胞系均高表达。IL-13RαmRNA表达率和表达丰度与胶质瘤分级（前者rs=0．87，P〈0．01；后者rs=0．69，P〈0．01）、肿瘤增殖活性Ki-67LI（r=0．64，P〈0．01）呈正相关，即胶质瘤恶性程度越高，IL-13RαmRNA表达率和表达水平越高。结论IL-13Rα基因在人脑胶质瘤中表达上升，与肿瘤的分级和肿瘤增殖活性呈正相关，可作为预测某些肿瘤治疗效果及监测复发的指标之一。