细胞因子在银屑病中的作用及中医药干预

银屑病是一种由T淋巴细胞(T lymphocyte,T)介导的免疫性皮肤疾病，以角质形成细胞异常增殖和炎症细胞浸润为特征。银屑病的发病机制十分复杂，各型细胞因子均参与银屑病的发病过程。细胞因子中以白介素(interleukin)、肿瘤坏死因子-α(tumor necrosis factor-α,TNF-α)、γ-干扰素(interferon-γ,IFN-γ)作用较为重要。各因子相互影响，形成网络状细胞因子通路。其中，肿瘤坏死因子、IFN-γ具有起始炎性反应的作用，通过炎性反应，增加作为银屑病发生发展的核心因子白介素17(interleukin-17,IL-17)的表达，同时上调促炎因子[TNF-α、IFN-γ、白介素-23(interleukin-23,IL-23)]、生长因子[(血管内皮生长因子(vascular endothelial growth factor,VEGF)、转化生长因子-β(transforming growth factor-β,TGF-β)]表达，引起细胞增殖及分化异常、炎症因子水平升高等病理性改变，共同构成银屑病患者体内炎性微环境。70%以上的患者会在此通路...     

TNF-α在抑郁症中的作用和机制研究

抑郁症是一种情感精神疾病,临床上以显著而持久的心境低落为主要特征。抑郁症严重危害人们身心健康,降低生活质量,增加社会负担。抑郁的产生原因比较复杂,发病机制存在多种假说。在过去的几十年,虽然对于抑郁症的研究取得了一定的进展,但其确切的病因及病理生理机制目前仍不明确。近期,研究显示,促炎性细胞因子,尤其是肿瘤坏死因子-α(tumor necrosis factor-α,TNF-α)在抑郁症的发生、发展及临床药理机制中扮演着重要角色。现通过对TNF-α的生物学特征、在抑郁症发病和抗抑郁治疗中的作用、基因多态性与抑郁症关联性以及未来的应用与展望等进行综述,以期从多方面阐明TNF-α在抑郁症中的作用。     

炎症诱发抑郁症：吲哚胺2,3 双加氧酶的激活是关键环节之一

本文通过回顾临床前期及临床期两阶段的文献,着重介绍炎症激活及抑郁症之间的相关联系并进一步探讨其机制。目前,抑郁症的机制研究热点之一是炎症反应又称为细胞因子假说,其中色氨酸--犬尿氨酸通路(KP)在该假说中的作用得到了越来越多的证实。该假说认为,色氨酸--犬尿氨酸途径是聚焦于抑郁症相关代谢产物改变的综合性通路。炎性抑郁症的产生是由于在免疫功能及神经递质改变下产生的炎性细胞因子激活了吲哚胺2,3-双加氧酶,从而进一步引发抑郁。吲哚胺2,3-双加氧酶的活性增加,不仅会导致色氨酸的衰竭同时还引起通过犬尿氨酸途径代谢的神经毒性产物的增加,而这两种改变都被认为与抑郁症的发病密切相关。在此基础上,我们主要聚焦于慢性病患者接受细胞因子治疗的相关研究,来探讨免疫激活病人中抑郁症发病的高风险性从而证明这一假说。这项工作的目的是希望通过对色氨酸--犬尿氨酸通路的研究,从吲哚胺2,3-双加氧酶的抑制,激活它的细胞因子的调节及寻找在犬尿氨酸途径中其它的靶点等方面来抗抑郁,从而为新型的抗抑郁药的发展提供新的方法途径。     

BDNF或5HTTLPR与抑郁症的研究

抑郁症是以抑郁为主要临床表征的一种精神疾病,近年抑郁症发病率正呈逐年上升趋势,如不加以干预,对患者及患者家庭、社会都会产生重大影响.对于抑郁症发病机制目前尚无定论,现有研究均停留在假说阶段.众多假说中脑源性神经营养因子(BDNF)和5-羟色胺转运体基因连锁多肽性区域(5-HTTLPR)参与抑郁症的病理生理过程,分别发挥重要作用,其基因也是抑郁症的候选基因,本研究对BDNF、5-HTTLPR在抑郁症及抗抑郁治疗等方面的作用进行文献综述.     

细胞因子在动脉粥样硬化发病中的作用机制及相关治疗举措研究现状

动脉粥样硬化是一种慢性炎症性疾病,开展细胞因子相关研究为动脉粥样硬化的预防和治疗提供了重要方向.细胞因子由不同类型的细胞产生,作用于一系列靶点,在动脉粥样硬化的发病和进展过程中起关键作用.本文概述了动脉粥样硬化有关的主要促炎和抗炎细胞因子及其作用机制,归纳了现阶段有关动脉粥样硬化细胞因子的针对性治疗措施,并对细胞因子在...     

致炎细胞因子在骨性关节炎病理生理中的作用

骨性关节炎(OA)是一种退行性病变,表现为关节软骨破坏,关节边缘骨赘形成,并伴有不同程度滑膜炎症,其病因学和发病机制还不是十分清楚。研究表明致炎细胞因子在骨性关节炎病发病的病理生理过程中起着重要的作用。本综述讨论目前关于致炎细胞因子在OA病理生理中的作用机制以及抗致炎细胞因子在治疗OA中的新进展。     

脱氢表雄酮调节炎性细胞因子作用的研究进展

炎症性疾病通常由过度或持续的炎症反应所引起。炎性细胞因子参与了炎症反应中的多个过程，如促进炎症细胞的聚集、诱导炎症介质的生成等。因此，控制炎性细胞因子的生成对炎症性疾病的治疗具有至关重要的作用。脱氢表雄酮(dehydroepiandrosterone,DHEA)是一种内源性类固醇激素。DHEA能调节炎性细胞因子的产生和释放，具有控制炎症反应的潜力。本文从DHEA的特征、调节炎性细胞因子的机制及临床应用前景进行综述，为临床治疗炎症性疾病提供新的思路和策略。     

预防性给予维生素D对实验性脑疟前炎症应答的影响

通过预防性给予维生素D(Vitamin D,VD)治疗,研究VD对实验性脑疟(ECM)模型鼠感染结局及免疫应答的影响,进一步阐明VD的免疫调节作用。通过P.b ANKA感染的C57BL/6小鼠建立ECM模型,通过ELISA和Griess法检测了预防给予VD对实验组小鼠脾上清和血清中前炎性细胞因子(IFN-γ、TNF-α和NO)和抗炎性细胞因子(IL-10)水平的影响,并检测了血脑屏障通透性的变化。结果显示,VD处理能够显著延长宿主生存期,同时显著降低血清和脾上清中的前炎性细胞因子水平,显著提升抗炎性细胞因子水平,从而保护血脑屏障完整性,进而抑制脑疟发生。结果表明,预防性给予VD治疗可以通过抑制宿主前炎症免疫应答以防止脑疟发生。     

阿尔采末病中的炎症反应

阿尔采末病 (Alzheimer病 )是常见的老年病之一 ,其发病机制尚不明确 ,但已有大量相关的实验结果和假说 ,其中脑内的免疫炎症反应是一个重要的方面。小胶质细胞和星形胶质细胞是参与脑内炎症反应的主要免疫细胞。小胶质细胞可吞噬淀粉样蛋白 ,激活补体系统 ,释放大量炎性介质 ,激活星形胶质细胞。星形胶质细胞活化后参与淀粉样蛋白和其他病理沉积物的吞噬 ,也释放某些炎性细胞因子 ,部分反馈性抑制小胶质细胞活性。此外 ,脑内的炎症反应还与环氧酶、磷脂酶及自由基等密切相关。目前包括抑制胆碱脂酶活性、抗氧化、抑制淀粉样蛋白生成及聚集等在内的治疗方案均不能达到理想的疗效 ,而流行病学调查和临床实验回顾表明部分非甾体抗炎药可以降低其发病危险性 ,因此开发疗效更好、特异性更强、副作用低的抗炎药物是较有前景的方向     

抑郁症的炎症机制及诊疗新策略

抑郁症是一类重要的精神心理疾病,其因高患病率、高致残性和高疾病负担等特征成为困扰全球的严重健康问题。一般认为,抑郁症的病因是多方面的,与性别差异、慢性应激、饮食行为方式及药物、酒精的滥用等有关。目前关于该疾病的具体病理生理机制仍未明确,研究者提出了诸如单胺能神经递质紊乱、下丘脑-垂体-肾上腺(hypothalamic-pituitary-adrenal,HPA)轴功能紊乱、神经营养因子以及细胞因子等学说。基于最新研究证据以及临床工作中传统抗抑郁药效果不佳的客观事实,细胞因子学说近年来备受关注。现阶段关于细胞因子在抑郁症发病中的作用与机制研究主要集中在促炎细胞因子,尤其是肿瘤坏死因子-α(tumor necrosis factor-α,TNF-α)、白细胞介素-1β(interleukin-1β,IL-1β)以及白细胞介素-6(interleukin-6,IL-6)等。随着国内外研究的深入开展,越来越多新分子、新机制被不断揭示。本文从炎症反应的角度对抑郁症发生和发展的病理生理机制进行综述,针对目前临床抗抑郁治疗的低应答率现状,提出新的诊疗策略,即抑郁症患者入院时检测炎症反应水平,对高炎患者联合使用抗炎治疗,旨在解决由于高炎状态导致应答率不理想的难治性抑郁症。     

Suppression of cytokine production by supernatants from CD8+ lymphocytes activated by mycobacterial fractions: The role of interleukins 4 and 6

Supernatants derived from CD8⁺ lymphocytes treated with mycobacterial components, or the partially purified carbohydrates from these supernatants, increased the production of IL-4 and IL-6 by mononuclear cells. The addition of anti-IL4 or anti-IL6 antibodies to LPS stimulated MN cells incubated with supernatants from CD8⁺ lymphocytes or carbohydrates resulted in the restoration of other cytokine production by these MN cells. Recombinant IL-4 and IL-6 on their own suppressed the production of IL-1, TNF-, IL-2 and IFN- by mononuclear cells. Such suppression could be reversed with antibodies to IL-4 and IL-6. The addition of rIL-4 and rIL-6 did not increase the suppression of cytokine production induced by suppressor supernatants or carbohydrates. Interleukin 4 decreased the production of IL-6 by MN cells; whilst IL-6 suppressed IL-4 production in a dose dependent manner. Both effects could be reversed with the appropriate antisera. Our results suggest that mycobacteria could evade host immunity by inducing the production of IL-4 and IL-6 by host mononuclear cells. These cytokines, in turn, would suppress the production of other cytokines necessary for effective cellular immunity.Abbreviations IL-1 interleukin 1 - IL-2 interleukin 2 - IL-4 interleukin 4 - IL-6 interleukin 6 - IFN- gamma interferon - TNF- tumour necrosis factor alpha - MN cells mononuclear cells - NAL's non-adherent lymphocytes - LPS lipopolysaccharide - PMA phorbol myristate acetate - RIA radioimmunoassay - ELISA enzyme-linked immunosorbent assay - rIL-4 recombinant interlukin-4 - rIL-6 recombinant interleukin-6 - U/ml units per millilitre - g/ml micrograms per millilitre - ng/ml nanograms per millilitre     

Chemokine‐guided cell migration and motility in zebrafish development

Chemokines are vertebrate‐specific, structurally related proteins that function primarily in controlling cell movements by activating specific 7‐transmembrane receptors. Chemokines play critical roles in a large number of biological processes and are also involved in a range of pathological conditions. For these reasons, chemokines are at the focus of studies in developmental biology and of clinically oriented research aimed at controlling cancer, inflammation, and immunological diseases. The small size of the zebrafish embryos, their rapid external development, and optical properties as well as the large number of eggs and the fast expansion in genetic tools available make this model an extremely useful one for studying the function of chemokines and chemokine receptors in an in vivo setting. Here, we review the findings relevant to the role that chemokines play in the context of directed single‐cell migration, primarily in neutrophils and germ cells, and compare it to the collective cell migration of the zebrafish lateral line. We present the current knowledge concerning the formation of the chemokine gradient, its interpretation within the cell, and the molecular mechanisms underlying the cellular response to chemokine signals during directed migration.     

Effects of inflammatory cytokines on bone/cartilage repair

Many inflammatory factors can affect cell behaviors and work as a form of inter-regulatory networks through the inflammatory pathway. Inflammatory cytokines are critical for triggering bone regeneration after fracture or bone injury. Also, inflammatory cytokines play an important role in cartilage repair. The synergistic or antagonistic effects of both proinflammatory and anti-inflammatory cytokines have a great influence on fracture healing. This review discusses key inflammatory cytokines and signaling pathways involved in bone or cartilage repair.     

Inhibition of collar-induced carotid atherosclerosis by recombinant apoA-I cysteine mutants in apoE-deficient mice

The previous studies in our laboratory revealed that seven cysteine mutants of apolipoprotein A-I (apoA-I) have different structural features and biological activities in vitro and in vivo. To investigate the potential cardioprotective effects of apolipoprotein A-I(N74C) [apoA-I(N74C)], we examined the anti-inflammatory, antioxidant, and antiatherosclerotic effects of this cysteine mutant in a rapid atherosclerosis model induced by perivascular carotid collar placement in apoE^−/− mice. Lipid-free apoA-I(N74C) showed a significant increased antioxidant potency in low density lipoprotein (LDL) oxidation in vitro and reduced intracellular lipid accumulation in THP-1-derived macrophages, relative to wild-type apoA-I (apoA-Iwt). Mice injected with recombinant HDL (rHDL) reconstituted with apoA-I(N74C) (named rHDL74) through tail veins (40 mg/kg of body weight, three injections) had a significant lower level of serum interleukin-6 (IL-6) and enhanced serum antioxidation compared with mice receiving rHDL reconstituted with apoA-Iwt (named rHDLwt). Moreover, compared with rHDLwt, the rHDL74 in vivo injection resulted in a significant decrease in plaque size, ratio of aorta intima to media, arterial remodeling, and macrophage content in lesions. In summary, intravenous injection with rHDL74 reconstituted with apoA-I cysteine mutant apoA-I (N74C) dramatically delays the development of atherosclerosis induced by perivascular carotid collar placement and reduces vascular remodeling in the carotid artery in apoE^−/− mice.     

Cytokine kinetics in the plasma of monkeys infected with pathogenic and nonpathogenic simian and human immunodeficiency chimeric viruses at an early stage of infection

To evaluate the pattern of cytokines as a result of pathogenic and nonpathogenic SHIV infections in monkeys, we analyzed the cytokines interleukin (IL)-2, IL-4, IL-10, IL-12, and interferon (IFN)-gamma in the plasma of 8 monkeys infected with either pathogenic 89.6P or nonpathogenic NM-3rN chimeric viruses. The cytokine kinetics in the 89.6P-infected monkeys was characterized by increases of IL-2, IL-10, and to some extent IFN-gamma and a decrease of IL-12. Although that of NM-3rN-infected monkeys was characterized by an increase of IFN-gamma, and a transient decrease of IL-12. IL-4 was not detected in any of the monkeys. The results, therefore, showed a mixture of Th-1 and Th-2 cytokine profiles implying these cytokines are not clear enough to use as an index of the pathogenicity of the viruses at an early stage of infection.     

Relative role of CSF-1, MCP-1/JE,and RANTES in macrophage recruitment during successful pregnancy

It has been previously demonstrated that macrophage colony stimulating factor (CSF-1) is produced by uterine epithelial cells in response to estrogen and progesterone. Studies in normal and op/op mice demonstrated that accumulation of a portion of the uterine macrophage population could be attributed to the chemotactic properties of CSF-1. Op/op mice exhibit greatly reduced rates of fertility, but successful pregnancy is not completely blocked. Also, uteri from op/op mice are not completely macrophage deficient. There are two possible explanations for this. One is that not all tissue macrophages are recruited from the bone marrow pool; some may be derived from primitive mesenchyme. Alternatively, tissue macrophages may be recruited from the bone marrow pool through expression of other type I chemokines such as JE, RANTES, MIP-1α, MIP-1β, IP-10, and KC. Both RANTES and JE are expressed at higher levels than CSF-1 during early pregnancy. The variable expression and relative role of these various chemokines in pregnancy was addressed by measuring mRNA expression during the first 8 days of pregnancy and in a pseudopregnant model. The expression of these various genes relative to macrophage numbers and macrophage distribution will be discussed. The relative role of these various factors in preparing the uterus for blastocyst implantation will be discussed. Mol Reprod Dev 46:62–70, 1997. © 1997 Wiley-Liss, Inc.     

Pro-inflammatory cytokines as emerging molecular determinants in cardiolaminopathies

Mutations in Lamin A/C gene (lmna) cause a wide spectrum of cardiolaminopathies strictly associated with significant deterioration of the electrical and contractile function of the heart. Despite the continuous flow of biomedical evidence, linking cardiac inflammation to heart remodelling in patients harbouring lmna mutations is puzzling. Therefore, we profiled 30 serum cytokines/chemokines in patients belonging to four different families carrying pathogenic lmna mutations segregating with cardiac phenotypes at different stages of severity (n = 19) and in healthy subjects (n = 11). Regardless lmna mutation subtype, high levels of circulating granulocyte colony-stimulating factor (G-CSF) and interleukin 6 (IL-6) were found in all affected patients’ sera. In addition, elevated levels of Interleukins (IL) IL-1Ra, IL-1β IL-4, IL-5 and IL-8 and the granulocyte-macrophage colony-stimulating factor (GM-CSF) were measured in a large subset of patients associated with more aggressive clinical manifestations. Finally, the expression of the pro-inflammatory 70 kDa heat shock protein (Hsp70) was significantly increased in serum exosomes of patients harbouring the lmna mutation associated with the more severe phenotype. Overall, the identification of patient subsets with overactive or dysregulated myocardial inflammatory responses could represent an innovative diagnostic, prognostic and therapeutic tool against Lamin A/C cardiomyopathies.     

Regulation of effector and memory CD8+ T cell function by inflammatory cytokines

Cells communicate with each other through the production and secretion of cytokines, which are integral to the host response to infection. Once recognized by specific cytokine receptors expressed on the cell surface, these exogenous signals direct the biological function of a cell in order to adapt to their microenvironment. CD8⁺ T cells are critical immune cells that play an important role in the control and elimination of intracellular pathogens. Current findings have demonstrated that cytokines influence all aspects of the CD8⁺ T cell response to infection or immunization. The cytokine milieu induced at the time of activation impacts the overall magnitude and function of the effector CD8⁺ T cell response and the generation of functional memory CD8⁺ T cells. This review will focus on the impact of inflammatory cytokines on different aspects of CD8⁺ T cell biology.