Welcome to the neighborhood: epithelial cell-derived cytokines license innate and adaptive immune responses at mucosal sites

Summary: There is compelling evidence that epithelial cells (ECs) at mucosal surfaces, beyond their role in creating a physical barrier, are integral components of innate and adaptive immunity. The capacity of these cells to license the functions of specific immune cell populations in the airway and gastrointestinal tract offers the prospect of novel therapeutic strategies to target multiple inflammatory diseases in which barrier immunity is dysregulated. In this review, we discuss the critical functions of EC-derived thymic stromal lymphopoietin (TSLP), interleukin-25 (IL-25), and IL-33 in the development and regulation of T-helper 2 (Th2) cytokine-dependent immune responses. We first highlight recent data that have provided new insights into the factors that control expression of this triad of cytokines and their receptors. In addition, we review their proinflammatory and immunoregulatory functions in models of mucosal infection and inflammation. Lastly, we discuss new findings indicating that despite their diverse structural features and differential expression of their receptors, TSLP, IL-25, and IL-33 cross-regulate one another and share overlapping properties that influence Th2 cytokine-dependent responses at mucosal sites.     

口服抑毒调平液对慢性乙型肝炎患者Th1/Th2细胞因子的调节作用

目的观察抑毒调平液对慢性乙肝患者Th1/Th2细胞因子的影响.方法60例慢性乙型肝炎(中度)患者按随机双盲原则分为治疗组、对照组(每组30例).两组分别口服抑毒调平液或安慰剂.收集治疗前、治疗后停药时及停药3月末空腹血清标本,用酶联免疫吸附法检测细胞因子白细胞介素-2、白细胞介素-4、白细胞介素-12、干扰素-γ.另选30例年龄、性别与治疗组、对照组无差异的正常人作正常组.结果治疗前治疗组、对照组患者血清IL-2、IFN-γ、IL-12的水平及IFN-γ/IL-4明显低于正常人(P＜0.05),IL-4的含量明显高于正常人(P＜0.05),治疗组与对照组患者间上述各项指标比较均无显著差异(P＞0.05);治疗后停药时、停药3月末治疗组IL-2、IL-12、IFN-γ、IFN-γ/IL-4的值持续增加(P＜0.05),IL-4持续下降(P＜0.05),而对照组无明显变化(P＞0.05).结论抑毒调平液上调血清中IL-2、IL-12、IFN-r的含量及IFN-γ/IL-4的比值,下调IL-4的含量,促使Th1/Th2分泌的细胞因子比值恢复平衡,至少维持治疗结束后3个月.     

脓毒症早期外周血细胞因子的变化与意义

目的 :探讨脓毒症早期外周血细胞因子变化的规律与意义。方法 :应用盲肠结扎穿孔 (CLP)复制脓毒症的病理模型 ,观察CLP后外周血细胞因子TNF α、IL 1β、IL 6、IL 10变化和心、肝、肺、肾功能及形态学损伤。结果 :在CLP模型上 ,血中TNF α浓度 3h开始升高 ,6h达到峰值水平 ;血清IL 1β水平 6h开始显著增高 ,2 4h达到峰值水平 ;血清IL 6水平 3h显著高于对照水平 ,12h达到峰值状态 ,至 72h显著低于对照水平 ;抗炎细胞因子IL 10在 2 4h开始显著高于对照值 ,4 8h达到峰值水平 ,至 72h恢复到对照水平 ;心、肾功能在 12h和肝功能于 2 4h出现显著改变。结论 :脓毒症早期存在外周血促炎细胞因子表达上调 ,多脏器功能不全与细胞因子表达失调有关     

继发性棘球蚴病小鼠体内细胞因子改变的研究

目的通过利用钙拮抗剂维拉帕米和阿苯哒唑单独及联合用药治疗小鼠继发性棘球蚴病的疗效观察,探讨小鼠体内细胞因子的变化趋势。方法小鼠被随机分成7组(维拉帕米、阿苯哒唑的单用组、维拉帕米和阿苯哒唑的联合用药组、对照组)。给予药物治疗90d后,小鼠眼球取血,检测血清IL-2、IL-10和IgE的含量。结果治疗90d后,小鼠血清IL-2、IgE含量与对照组相比有显著性差异(P<0.05),IL-10的含量与对照组比无明显差异。结论IgE、IL-2和IL-10可以作为判断治疗棘球蚴病疗效的指标。     

Influence of Traditional Chinese Medicine Qingjieling on LFA-1-Dependent Leukocyte Adhesion to Endothelial Cells

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The cytokine-mediated imbalance between coagulant and anticoagulant mechanisms in sepsis and endotoxaemia

Disseminated intravascular coagulation (DIC) is a frequently occurring complication of sepsis and may contribute to multiple organ failure. More insight into the pathogenesis of this derangement of the coagulation system is necessary to develop more effective therapeutic strategies for this condition. Recently, more detailed knowledge on the pathogenetic pathways involved in DIC has been obtained by the study of models of experimental bacteraemia and endotoxaemia in human subjects and non-human primates. The mechanisms that lead to activation of coagulation, potentiated by the simultaneous depression of physiological inhibitory systems and to impaired function of the fibrinolytic system, are outlined in this review. In addition, the mediatory role of various cytokines in the derangement of coagulation is discussed.     

Kinetics of serum cytokines in adults undergoing peripheral blood progenitor cell transplantation

Summary. We investigated the serum cytokine levels (G-CSF, GM-CSF, IL-l/?, IL-3 and IL-6) using an ELISA in 14 patients with haematological malignancies undergoing peripheral blood progenitor cell transplantation (PBPCT). Serum G-CSF levels in all patients rose immediately after PBPCT, then gradually decreased as the neutrophil counts began to rise. No detectable serum levels of GM-CSF or IL-lp were observed, but serum levels of IL-3 rose transiently immediately following PBPCT. Serum levels of JL-6 rose transiently during a fever in four patients. These observations suggest that G-CSF and L 3 may contribute to the early haemopoietic reconstitution in PBPCT.     

Interleukin-6 Does Not Stimulate Rat Myometrial Contractions in an In Vitro Model

PROBLEM: Interleukin-6 (IL-6) is increased in culture-positive amniotic fluid in women with preterm labor. IL-6 stimulates the production of prostaglandins leading to increased uterine activity. METHODS: We tested the hypothesis that IL-6 increases myometrial activity through release of uterotonic mediators. We studied the effect of IL-6 on uterine contractions in the absence and presence of fetal membranes to determine if the effect was on myometrium alone or was mediated through fetal membranes/decidua. IL-6 in concentrations of 100, 10, 0.1 or 0 ng/ml was added to the maternal side of the dual chamber-fetal membrane-uterine muscle in vitro model. RESULTS: We found that 10 ng/ml of IL-6 alone, without fetal membranes, caused a significant decrease in uterine contractions over time (P≤0.01). This decrease was not observed with the addition of term, nonlabored fetal membranes. CONCLUSIONS: IL-6 in the presence or absence of membranes, over a four log fold dose range, did not stimulate uterine contractions.     

House dust mite immunotherapy results in a decrease in Der p 2-specific IFN-γ and IL-4 expression by circulating T lymphocytes

Background Allergen-specific immunolherapy (IT) can be an important adjunctive therapy in the treatment of allergic disorders. Although it has now been used for over 80 yr. the precise mechanism of action remains unclear. Recently a number of studies have shown that cytokine production may be modified by IT, but different protocols have been used and different results obtained. Objectives The aims of the present study were: (1) lo document the allergen-specific expression of intcrleukin-4 (IL-4) and interferon-γ (IFN-γ) by peripheral blood cells in both untreated house dust mite (HDM) allergic patients(non-lT) and following at least 10 months of HDM-specific IT (post-IT); and (2) to determine whether alterations in these critical regulatory cytokines correlated with the clinical outcome of IT. Methods IT was undertaken with nine fortnightly subcutaneous injections of increasing amounts of a Dertnatophagoides pteronyssinus (Dpt) extract, reaching a final dose of 10000 PNU. This was followed by 6- to 8-monthly maintenance injections of 5000 PNU. For cytokine measurement, mononuclear cells were separated from peripheral blood and stimulated with the major Dpt allergen, Der p 2. for 18 h, after which mRNA was isolated and IL-4 and IFN-γ cDNA were amplified by polymerase chain reaction (PCR). The presence of the particular cytokine was determined by visualization following clcctrophoresis on an agarose gel. The study was observational in nature being open and without a placebo group. Results Fifteen Dpt-sensitive patients who had not received HDM IT (non-IT), and 16 who had, were studied. In the non-IT group. 80% expressed IL-4 and 75% expressed IFN-γ. In those post-IT, only 12.5% expressed IL-4 and 19% IFN-γ. The two patients still expressing IL-4 post-IT had had very little clinical response. Six patients were studied both pre- and post-IT. Prior to IT, three were positive for both cytokines, two positive for IL-4 alone and one for IFN-γ. Post-IT, all six were negative for IL-4 and five were negative for IFN-γ. Conclusion Allergen-specific IT results in a reduction in expression of the critical eytokines IL-4 and IFN-γ in circulating lymphocytes. It is possible that this is a contributary mechanism in the beneficial effect of IT.     

扶正祛邪颗粒对呼吸道病毒感染预防作用的临床研究

目的 观察扶正祛邪颗粒对呼吸道病毒易感人群免疫细胞及其因子的影响。方法 观察对象分别来源于2003年5-6月上海市25家医院呼吸道病毒易感人群（共1402名）,分别给予扶正祛邪颗粒（干预组）和安慰剂（对照组）,同时对干预组130名和对照组120名于服药前、服药2周及服药结束后2周测定血清干扰素γ（γ-IFN）、白细胞介素2、4（IL-2、4）及全血淋巴细胞分类计数（CD3^＋、CD4^＋、CDB^＋、B）和自然杀伤细胞（NK）细胞百分比。结果 在服药2周时,干预组血清中IL-2、γ-γIFN水平及NK细胞百分比较服药前明显升高（P〈0．05）,血清IL-4水平和CD3^＋、CD4^＋、CD8^＋及B细胞百分比无明显变化;服药2周及服药后2周干预组Th1／Th2较服药前和对照组明显升高（P〈0．05）。结论 扶正祛邪颗粒在一定程度上能提高上呼吸道病毒易感人群的免疫功能。