T淋巴细胞亚群及Th1/Th2细胞因子谱早期鉴别细菌尿源性脓毒症

目的探究尿源性脓毒症患者T淋巴细胞亚群及辅助性T细胞1(Th1)/Th2细胞亚群细胞因子谱水平变化及其对革兰阳性菌、革兰阴性菌的鉴别价值。方法选择2015年2月-2020年3月遵义医科大学附属医院收治的98例尿源性脓毒症患者、80例常规泌尿系统感染患者及100名查体的健康志愿者作为研究对象,分别纳入脓毒症组、局部感染组、对照组。对脓毒症组患者进行病原菌分析,检测T淋巴细胞亚群比例及白细胞介素-2(IL-2)、IL-4、IL-6、IL-10、肿瘤坏死因子(TNF-α)、干扰素-γ(IFN-γ)等细胞因子水平。结果入组脓毒症患者中,革兰阴性菌引起的尿源性脓毒症患者共53例(检出革兰阴性菌53株),以大肠埃希菌、肺炎克雷伯菌、铜绿假单胞菌为主;革兰阳性菌引起的尿源性脓毒症患者共45例(检出革兰阳性菌45株),以表皮葡萄球菌、粪肠球菌、金黄色葡萄球菌、溶血葡萄球菌为主。脓毒症组患者CD₃⁺T淋巴细胞亚群比例、CD₄⁺T淋巴细胞亚群比例、CD₄⁺/CD₈⁺分别为(59.84±7.41)%、(34.84±5.26)%、(1.42±0.65),低于局部感染组、对照组,而IL-2、IL-4、IL-6、IL-10、TNF-α、IFN-γ分别为2.69(0.98,16.23)pg/ml、2.49(0.74,22.74)pg/ml、88.41(10.24,188.52)pg/ml、25.63(1.74,74.15)pg/ml、3.25(1.01,16.96)pg/ml、7.11(1.22,15.63)pg/ml,高于局部感染组、对照组(P<0.05)。革兰阳性菌感染患者CD₃⁺、CD₄⁺、CD₄⁺/CD₈⁺分别为(64.15±4.71)%、(37.41±5.41)%、(1.53±0.34),高于革兰阴性菌感染患者,IL-6、IL-10、TNF-α分别为70.12(15.26,152.37)pg/ml、10.89(2.22,35.96)pg/ml、2.88(1.01,15.27)pg/ml,低于革兰阴性菌感染患者(P<0.05)。CD₃⁺、CD₄⁺、CD₄⁺/CD₈⁺、IL-6、IL-10等指标鉴别革兰阳性菌感染及革兰阴性菌感染的曲线下面积分别为0.651、0.681、0.656、0.769、0.758,当截点值为61.70%、35.10%、1.47、77.41 pg/ml、17.16 pg/ml时约登指数最大。结论尿源性脓毒症患者存在T细胞亚群及Th1/Th2细胞因子谱水平的失衡,且革兰阳性菌及革兰阴性菌脓毒症患者存在一定差异,临床可根据这些指标进行早期诊断及病原菌类型的鉴别。     

Antigen-specific production of interleukin (IL)-13 and IL-5 cooperate to mediate IL-4Ralpha-independent airway hyperreactivity

The pathogenesis of human asthma and the development of key features of pulmonary allergy in mouse models has been critically linked to IL-13. Analyses of the receptor components employed by IL-13 have shown that delivery of this cytokine to the airways of naive IL-4Ralpha gene targeted (IL-4Ralpha(-/-)) mice fails to induce disease, suggesting that this membrane protein is critical for transducing IL-13-mediated responses. The current study demonstrates that, in contrast to naive mice, T helper 2 bias, airways hyperreactivity (AHR) and tissue eosinophilia develop in Ovalbumin-sensitized IL-4Ralpha(-/-) mice and that these responses can be inhibited by the IL-13 antagonist sIL-13Ralpha2Fc. Therefore, antigen stimulation induces an IL-13-regulated response that is independent of IL-4Ralpha. To determine the role of IL-5 and eosinophils in the development of disease in antigen-exposed IL-4Ralpha(-/-) mice, pulmonary allergy was examined in mice deficient in both factors. IL-4Ralpha/IL-5(-/-) mice were significantly defective in their ability to produce IL-13 and failed to develop AHR, suggesting that IL-5 indirectly regulates AHR in allergic IL-4Ralpha(-/-) mice by an IL-13-dependent mechanism. Collectively, these results demonstrate that IL-13-dependent processes regulating the development of AHR and T helper bias persist in the in the lungs of allergic IL-4Ralpha(-/-) mice.     

化解冲剂对脓毒症大鼠神经肽及细胞因子的调节作用

为阐明传统中医学整体观与现代医学神经内分泌免疫网络学说的一致性。建立了大鼠用人感染模型；动态观察了脓毒症大鼠血浆中β－内啡肽、精氨酸加压素及血管活性肠肽的变化；同时观察了血中单个核细胞分泌肿瘤坏死因子α及白细胞介素６能力的改变；并观察了活化瘀代表方剂“化解冲剂”对上述改变的调节作用。     

透析器复用对补体及单个核细胞激活的影响

目的：了解透析器复用对补体和单个核细胞激活的影响。方法：比较透析器第四次复用与首次使用时,血浆补体终末复合物（SC5b-9）浓度及分离的单个核细胞（PBMC）在体外培养产生IL－1β、TNF-α和IL－6量的差异。结果：血仿膜透析器用过氧乙酸和福尔马林消毒后第四次复用时,血浆SC5b-9浓度变化幅度较首次使用明显降低;PBMC在LPS刺激下体培养产生IL－1β、TNF-α和IL－6的量与首次使用相比差异无显著性。结论：血仿膜透析器用过氧乙酸和福民林消毒复用,可在一定程度上降低其补体激活能力,但不影响PBMC产生细胞因子。     

TNFa、IL6与肝储备功能关系的探讨

目的 :探讨外周血中TNFa、IL6与肝功能之间的关系 ,了解TNFa、IL6预测肝储备功能的方法可行性。方法 :采用放射免疫分析法测量 84例肝脏外科疾病的病人 (梗阻性黄疸 5 9例 ;肝硬化门脉高压 10例 ;肝癌 15例 )。外周血中TNFa和IL6的浓度。同时病人行常规肝功检测。结果 :肝病组外周血清中TNFa、IL6的浓度比对照显著升高 ,肝病组为TNFa13 .35± 5 .14(fmol l) ;IL6为 2 40 .6 2± 70 .17(pg l)对照组TNF为 6 .2 1± 2 .0 3(fmol l) ,IL为 93.75± 40 .5 7(pg l)肝病组与对照组比较 ,TNFa和IL6的P值均 <0 .0 1;肝功能越差TNFa越高 ,且在肝功A级、B级、C级三级间两两比较亦有差异P <0 .0 5。结论 :外周血中TNFa和IL6可作为肝功能损害的一种标记物     

The pathogenesis and modulation of the post-treatment reactive encephalopathy in a mouse model of Human African Trypanosomiasis

Drug treatment of late-stage human African Trypanosomiasis (HAT) in which the central nervous system (CNS) is involved may be complicated by a severe post-treatment reactive encephalopathy (PTRE) which can be fatal in up to 10% of cases. In order to understand the immunopathogenesis of this complication, an experimental mouse model has been developed that mirrors many of the pathological features of the PTRE in humans, and which allows various anti-inflammatory therapeutic regimes to be evaluated. Following the development of the PTRE in this model a number of cytokines are increased within the CNS including tumour necrosis factor (TNF) alpha, interleukins 1, 4 and 6, and macrophage inflammatory protein (MIP)-1. These cytokines appear at the same time as astrocyte activation which is an early event occurring before the development of the marked meningoencephalitic inflammatory response. The immunosuppressant drug azathioprine prevents but does not reduce the severity of an established PTRE and has a minimal effect on astrocyte activation. The ornithine decarboxylase inhibitor eflornithine prevents the induction, and ameliorates the severity, of the PTRE, and also reduces the degree of astrocyte activation. The Substance P antagonist RP-67,580 ameliorates the severity of an established PTRE, and also reduces astrocyte activation, indicating an important role of SP in the generation of the inflammatory response. Continued use of this mouse model should lead to further enhancement of our understanding of the pathogenesis of the PTRE and to improved drug regimes to prevent and/or treat it.     

Effects of antipsychotic drugs on cytokine networks

It has been known since the 1950s that phenothiazines have immunomodulatory effects. This review summarizes recent evidence suggesting that antipsychotic drugs, in particular chlorpromazine and the atypical compound clozapine, influence the production of cytokines. Cytokines, organized in networks of related peptides with pleiotropic functions, are pivotal humoral mediators of infection and inflammation, and they play an important role in hematopoiesis and autoimmunity. Therefore, the effects of antipsychotic drugs on cytokine networks are important for the understanding of immune-mediated side effects of these drugs, e.g. agranulocytosis. In addition, modulation of cytokine production by antipsychotic agents suggests that these drugs might be useful for the treatment of diseases which primarily involve the immune system. Moreover, because cytokines are known to have numerous effects on the CNS, they may mediate effects of antipsychotic drugs on brain functions. Finally, the influence of antipsychotic drugs on cytokine networks is an important confounding factor in studies investigating disease-related immunopathology in psychiatric disorders. This review provides a synopsis of the data published on these topics and outlines future research perspectives.