EFFECT OF CYTOKINES IN HOST DEFENSE AND INFLAMMATION

细胞因子在宿主防御和炎症中的作用

• 批准号: 5200490
• 负责人: J I GALLIN
• 金额: --
• 依托单位: NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/5200490
• 关键词: Actinomycetales infection; adolescence (12-20); blister; child (0-11); chronic granulomatous disease; cytokine; human subject; hyperglobulinemia; immunotherapy; inflammation; interleukin 8; microorganism immunology; neutrophil; tumor necrosis factor alpha

Studies were performed to define the accumulation of cytokines and other mediators of inflammation in experimental models of inflammation in normal human subjects and in patients with abnormalities of host defenses or inflammation. Skin blisters created by suction and heat were used to study local inflammation in the skin. This blister system has been used by us to characterize the accumulation of inflammatory mediators. Studies of skin blisters in patients with abnormal inflammatory responses revealed dramatic increases in TNF-alpha in patients with acute vasculitis in association with Wegeners granulomatosis, in patients with systemic mastocytosis, and in the syndrome of hyperimmunoglobulin E and recurrent infections (Job's syndrome). Increases in TNF-alpha correlated well with disease activity suggesting that targeting drug development for modulation of this cytokine will have specific merit in these disease states. Normal blister exudate neutrophils synthesize large amounts of IL-8, compared with control peripheral blood neutrophils. Studies of normals and patients with excessive inflammation revealed a tight linear relationship between the level of IL-8 and the number of inflammatory neutrophils in the exudate. Exudate neutrophils synthesize IL-8 which is stored in a compartment different from specific or azurophil granules, but is co-eluted with an alkaline phosphatase rich plasma membrane fraction. Exposure of blood neutrophils to the calcium ionophore A23187 mimicked exudation and increased neutrophil IL-8 concentration 200-fold.

进行研究以确定细胞因子和其他细胞因子的积累。 实验性炎症模型中的炎症介质 正常人受试者和宿主防御异常的患者 或炎症。 通过抽吸和加热产生的皮肤水泡用于 研究皮肤的局部炎症。 该泡罩系统已被用于 来表征炎症介质的积累。 异常炎症反应患者皮肤水疱的研究 在急性胰腺炎患者中， 与韦格纳肉芽肿病相关的血管炎， 系统性肥大细胞增多症，以及高免疫球蛋白E综合征， 复发性感染（Job’s syndrome） TNF-α的增加与 以及疾病活动表明，靶向药物开发， 这种细胞因子的调节在这些疾病中具有特殊的优点 states. 正常水疱渗出液中性粒细胞合成大量的 IL-8，与对照外周血中性粒细胞相比。 研究 正常人和过度炎症的患者显示出紧密的线性关系， IL-8水平与炎性细胞数的关系 渗出液中有中性粒细胞 渗出液中性粒细胞合成IL-8， 储存在不同于特定或嗜天青颗粒的隔室中， 但与富含碱性磷酸酶的质膜共洗脱 分数 血液中性粒细胞暴露于钙离子载体A23187 模拟渗出并使中性粒细胞IL-8浓度增加200倍。