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.     

尖锐湿疣患者的细胞免疫功能研究

目的探讨尖锐湿疣患者细胞免疫功能状态,并为其免疫治疗提供实验依据。方法采用流式细胞仪检测外周血T细胞亚群和NK细胞百分比、MTT法检测淋巴细胞的增殖能力、ELISA法检测血清中细胞因子。结果CA患者外周血中CD3+、CD4+、CD4+/CD8+和CD56+细胞(NK细胞)的比例均明显低于对照组(均P<0.01);CA组血清中IL-12和IFN-γ产生水平均明显低于对照组(均P<0.01);而IL-10产生水平高于对照组(P<0.01);CA患者的PBMC对PHA四种诱导浓度的增殖能力均明显低于对照组(均P<0.01);CA患者的RBC-C3bRR的百分率明显低于对照组(P<0.01),而RBC-ICR百分率明显高于对照组(P<0.01)。结论CA患者存在细胞免疫功能缺陷,临床治疗过程中须提高CA患者的细胞免疫功能。     

细胞因子网络--抗银屑病药物的分子免疫学靶位

从分子免疫学的角度阐述了细胞因子异常、细胞因子网络失衡等与银屑病发病的关系，并介绍了针对细胞因子网络设计抗银屑病药物的研究现状，为人们寻找抗银屑病药物提供新线索。     

Expression of immunoregulatory cytokines in neurons of the lateral hypothalamic area and amygdaloid nuclear complex of rats immunized against human IgG

Present results showed that interleukin-1 (IL-1), IL-6 and transforming growth factor-beta (TGF-beta) were constitutively expressed in the supraoptic and paraventricular nuclei of the rat hypothalamus. Immunoreactive cells were also detected, but to a lesser extent, in other parts of hypothalamus as well as in the cerebral cortex. In rats immunized with IgG, there was moderate increase in immunoreactivities of the cytokines. A notable feature, however, was the induction of the cytokine expression in the lateral hypothalamic area and the amygdaloid nuclear complex, suggesting that the neurons in these two areas are involved in possible immune regulation.     

Wistar大鼠树突状细胞的体外培养、扩增与鉴定

目的：探讨体外分离、培养和扩增大鼠骨髓来源树突状细胞（DC）的有效方法。方法：采用改良的Chen－WoanDC培养方法，梯度离心提取骨髓单核细胞中的非粘附细胞，加入GM CSF 5?ng/ml、IL 4 5?ng/ml进行诱导扩增，对培养的目的细胞进行形态学、OX62－FITC免疫荧光检查以及功能学鉴定。结果：DC前体细胞培养10?d呈典型树突状结构，表面标志物染色阳性，流式细胞学检查OX62单抗阳性率86％，不同培养时段的DC诱发混合淋巴细胞反应以培养10?d的DC最强，培养10?d的DC诱发混合淋巴细胞反应对同源淋巴细胞有更好的活性。结论：改良的Chen－Woan法为体外诱导扩增大鼠骨髓来源DC的有效方法。     

充血性心力衰竭患者细胞免疫功能失调的探讨

目的探讨充血性心力衰竭(CHF)患者外周血辅助性T淋巴细胞功能失调及其在心力衰竭发生及发展中的意义。方法选择62例CHF患者作为研究组,其中,心功能Ⅱ级28例,Ⅲ级16例,Ⅳ级18例;30例健康志愿者作为对照组。采用流式细胞分析法,检测所有被检者外周血CD4 细胞胞内细胞因子干扰素γ(IFN-γ)和白细胞介素4(IL-4)的表达。同时分离外周血单个核细胞,经植物血凝素(PHA)刺激培养后,应用酶联免疫吸附方法(ELISA)检测培养上清液中IFN-γ和IL-4水平。结果CHF组患者IFN-γ染色阳性的细胞占CD4 T细胞的比率为17.48%,明显高于对照组的12.09%。IL-4染色阳性细胞比率两组间未见显著差异。ELISA检测显示心力衰竭组培养上清液中IFN-γ水平及IFN-γ/IL-4比值明显高于对照组,而两组间IL-4水平则无显著差异。结论心力衰竭患者辅助性T淋巴细胞功能与心功能之间有一定关系,辅助性T淋巴细胞功能失调可能参与了CHF患者的心室重构过程。