C‐reactive protein and tumor necrosis factor‐alpha in relation to insulin‐mediated glucose uptake,smoking and atherosclerosis

Objectives. To examine the hypothesis that serum concentration of C‐reactive protein (CRP) is inversely associated with insulin sensitivity and obesity, and that this may by mediated by tumor necrosis factor‐α (TNFα) and interleukin‐6 (IL‐6). Material and methods. Cross‐sectional, one‐center study of a population‐based sample of 58‐year‐old Swedish men (n = 98). Exclusion criteria were cardiovascular disease, clinical diabetes mellitus and/or continuous cardiovascular medication. Glucose infusion‐rate (euglycemic hyperinsulinemic clamp), adjusted for fat‐free mass, which together with total body fat was measured by dual‐energy X‐ray absorptiometry. Serum concentrations of CRP, TNFα, soluble TNFα receptor 2 (sTNFAR2), IL‐6 determined by ELISA. Ultrasound was used to measure intima‐media thickness (IMT) in both common carotid arteries, carotid bulbs and in the right femoral artery. Results. CRP was inversely associated with insulin sensitivity (r = ?0.28, p<0.01) and with total body fat (r = 0.31, p<0.01), but not independently of the TNFα and sTNFAR2 product. Serum CRP, TNFα, sTNFAR2, but not IL‐6, were associated with low insulin sensitivity, total body fat, abdominal obesity, hyperinsulinemia, hypertriglyceridemia, low HDL cholesterol and small LDL particles, i.e. the metabolic syndrome. These associations were independent of smoking and carotid and femoral artery IMT. Conclusions. Serum concentrations of CRP were related to insulin sensitivity and accompanying factors constituting the metabolic syndrome. The results indicate that this association may be mediated by adipose tissue and TNFα effects, the latter measured as the product of TNFα and sTNFAR2. This was a cross‐sectional study and causality cannot be proven.     

原核表达重组人白介素-3及其对脐带血造血干细胞体外增殖的影响

目的研究原核表达重组人白介素-3(rhIL-3)及其对脐带血造血干细胞体外增殖的影响。方法构建pET-43.1-rhIL-3表达载体,克隆至BL21菌株,并进行中试发酵生产,所得包涵体经透析复性后,采用阳离子交换柱纯化,纯化产物送N-端测序。Ficoll密度梯度离心结合免疫磁珠法富集人脐带血中CD34+细胞,以不同浓度rhIL-3及干细胞因子(SCF)、Fms样酪氨酸激酶受体-3配体(FL)和促血小板生成素(TPO)因子组合培养1周,测定细胞总数,计算CD34+细胞增殖倍数。结果在SCF和FL存在下,rhIL-3可明显促进造血干祖细胞增殖,但较无rhIL-3时CD34+细胞占细胞总数的比例有所下降。与SCF、FL共同作用时的最佳浓度在15 ng/mL左右,与SCF、FL、TPO共同作用时的最佳浓度在50 ng/mL左右。结论高效表达及纯化的rhIL-3与SCF、FL和TPO细胞因子组合对脐带血造血干细胞具有良好的增殖作用。     

Targeting of eosinophils in asthma

Severe asthma continues to be an important source of morbidity despite the availability of bronchodilators and corticosteroids. Although new treatments are needed, better identification of asthma phenotypes may improve treatment effectiveness. One phenotype that has emerged is eosinophilic asthma. Eosinophils in asthma have been studied for many years, and the evidence suggests they play a major role in some forms of asthma. Eosinophilic asthma can be diagnosed using peripheral blood, sputum eosinophil count or exhaled nitric oxide. Depletion of eosinophils can be achieved by corticosteroids, specific anti-interleukin 5 (IL-5) or anti-IL-5-receptor-alpha therapies, or anti-immunoglobulin E approaches. This editorial refers to the approaches that are being taken in eosinophilic asthma with emphasis on the new investigational anti-IL-5-receptor-alpha antibody, benralizumab.     

白细胞介素-18逆转录病毒载体的构建及抗乙型肝炎病毒的研究

研究鼠白细胞介素－18（IL－18）基因的转移、表达及其抗乙型肝炎病毒（HBV）的作用。以逆转录聚合酶链反应（RT－PCR）技术从受植物凝血素（PHA）和脂多糖（LPS）刺激BALB/c小鼠脾脏细胞中扩增出IL－18的cDNA，并构建表达IL－8基因的重组逆转录病毒载体pLXSN-IL-18，转染PA317细胞，以逆转录巢式RT－PCR方法，验证细胞培养液上清分泌的假病毒颗粒中IL－18的表达，将假病毒颗粒感染2．2．15细胞，酶联免疫吸附法（ELISA）检测其上清HBsAg和HBeAg，定量检测HBV DNA。成功克隆出580bp的小鼠IL－18全基因并构建逆转录病毒载体，在转染PA317细胞的上清中检测出含IL－18假病毒颗粒，上清感染2．2．15细胞后第3、5、7、14天，HBsAg、HBeAg逐渐下降，到14天时HBsAg已变为阴性，对HBV DNA有明显抑制作用。IL－18能成功地在逆转录病毒载体中表达，并有抑制HBsAg、HBeAg表达的作用。     

口服米索前列醇联合宫腔吸引管在剖宫产术后无痛人流的应用

分析口服米索前列醇联合宫腔吸引管治疗剖宫产术后无痛人流的临床效果及机制。120例患者随机分为对照组(n=60)和观察组(n=60)。对照组患者接受宫腔吸引管处理,观察组患者口服米索前列醇(0.6 mg)后接受宫腔吸引管。结果显示观察组患者的手术时间和苏醒时间明显缩短(P<0.05),术中出血量和异丙酚用量明显减少(P<0.05);观察组患者的宫颈扩张效果总有效率明显升高(P<0.05)而不良反应发生率明显降低(P<0.05);两组患者治疗后血清中白细胞介素1β(IL-1β)和IL-2水平明显升高,且对照组患者的上述白细胞介素水平升高更显著(P<0.05)而雌激素促黄体生成素(Luteotropic hormone,LH)、促卵泡激素(Follicle stimulating horman,FSH)和雌二醇(Estradiol,E2)水平无明显变化(P>0.05)。实验表明口服米索前列醇联合宫腔吸引管治疗剖宫产术后无痛人流临床效果明显,且不引起白细胞介素和雌激素水平的剧烈变化。     

Evaluation of interleukin-6 and interleukin-10 in lung transplant patients with human cytomegalovirus infection

Abstract:  We hypothesized that interleukin-6 (IL-6) in plasma and bronchoalveolar lavage (BAL) might serve as additional diagnostic parameter in lung transplant patients with human cytomegalovirus (HCMV) infection. Therefore, we compared IL-6 levels in HCMV-positive vs. HCMV-negative patients. IL-6 was measured by ELISA in plasma and BAL in 111 patients. Furthermore, we investigated the influence of IL-10 on IL-6 production in HCMV-positive patients. For HCMV–DNA detection in plasma and BAL a quantitative polymerase chain reaction (PCR) assay was used. IL-6 levels were significantly higher in the HCMV-positive group (n = 39; BAL p = 0.045; plasma p = 0.017) in comparison to the HCMV-negative group (n = 72). IL-10 did not correlate with IL-6 concentration (p = 0.146). Donor (D) or recipient (R) HCMV-constellation did not influence IL-6 concentration. IL-6 levels were not influenced by elevated levels of HCMV copies. Our data suggest that IL-6 does not serve as a good diagnostic parameter for existence of HCMV infection in lung transplant patients. Because of the wide range of the IL-6 levels in both groups, we were not able to find a breakpoint differentiating between infected and not-infected patients. Another important finding was that IL-6 production is not dependent of the HCMV status of D/R.     

+Gz重复暴露大鼠脑组织中IL-1β和TNF-α mRNA表达变化

目的 了解反复高＋Ｇｚ暴露后大鼠脑组织中ＩＬ－１β和ＴＮＦ－αｍＲＮＡ表达变化。方法 ２０只ＳＤ大鼠随机分成对照组、＋Ｇｚ重复暴露后３０ｍｉｎ、６ｈ、２４ｈ和４８ｈ五组,每组４只,对照组大鼠Ｇ值为＋１Ｇｚ,实验组大鼠在动物离心机上经历了３次＋１４Ｇｚ／４５ｓ（两次间间隔３０ｍｉｎ）作用。分别于暴露后３０Ｇｚ,实验组大鼠在动物离心机上经历了３次＋１４Ｇｚ／４５ｓ（两次间间隔３０ｍｉｎ）作用,分别于暴     

Anti-inflammatory cytokine response and the development of multiple organ failure in severe sepsis

BACKGROUND: The production of proinflammatory cytokines activates the systemic inflammatory response in sepsis. Patients also develop a compensatory anti-inflammatory reaction, which may have an important down-regulatory effect on the overactive inflammation. However, the role of this anti-inflammatory response in sepsis is not completely clarified. In this prospective study, we investigated the relationship between the pro- and anti-inflammatory cytokine profiles in severe sepsis and their role in the development of multiple organ failure (MOF). METHODS: Thirty-eight patients meeting the criteria for severe sepsis were studied. MOF was defined as a maximum SOFA score of 10 or higher. Serial measurements of the proinflammatory IL-6 and IL-1beta and the anti-inflammatory IL-10 and IL-1ra were used. The cytokine samples were taken at the onset of sepsis and on the third and fifth day during the ICU period. RESULTS: The initial IL-10 and IL-1ra responses were identical in patients with or without MOF. The anti-inflammatory cytokine levels remained elevated in the MOF patients, whereas in patients without MOF the levels declined. The IL-6/IL-10 ratio was significantly higher in the MOF patients on days 1 and 3 compared with patients without MOF. CONCLUSIONS: We could not demonstrate overproduction of anti-inflammatory IL-10 in MOF patients. On the contrary, the high IL-6/IL-10 ratio indicates that IL-10 deficiency may contribute to the development of MOF in severe sepsis.