EFFECT OF CYTOKINES IN HOST DEFENSE AND INFLAMMATION

进行研究以确定细胞因子和其他 大鼠实验性炎症模型中的炎症介质 正常人和宿主防御异常患者 或者发炎。吸入和加热产生的皮肤水泡被用来 研究皮肤的局部炎症。该泡罩系统已投入使用。 我们用来描述炎症介质积聚的特征。 炎症反应异常患者皮肤水泡的研究 急性脑梗塞患者血清肿瘤坏死因子-α水平显著升高 与Wegeners肉芽肿相关的脉管炎 全身性肥大细胞增多症，以及高免疫球蛋白E和 反复感染(约伯氏综合征)。相关的肿瘤坏死因子-α的增加 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将具有特殊的优点 各州。正常水泡渗出的中性粒细胞合成大量的 IL-8，与对照组外周血中性粒细胞比较。的研究 正常人和过度炎症的患者显示出紧密的线性关系 白介素8水平与炎性细胞数量的关系 渗出液中的中性粒细胞。渗出性中性粒细胞合成IL-8， 储存在与特定或亲天青颗粒不同的隔室中， 但与富含碱性磷酸酶的质膜共洗脱 分数。血中性粒细胞对钙离子载体A23187的暴露 模拟渗出，使中性粒细胞IL-8浓度增加200倍。

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.