EFFECT OF CYTOKINES IN HOST DEFENSE AND INFLAMMATION

细胞因子和炎症介质的产生动力学 在正常受试者和选定的异常患者中进行检测 主场防守。在这项研究中，皮肤的炎症模型是 使用起泡装置的。在此之前，我们展示了在正常情况下 受试者C5a和LTb4在起泡后3小时内出现，I1-8和 IL-6在8~24小时出现，IL-1-B、GM-CSF、TNF-α在8~24小时出现 出现时间从12小时到24小时。最近我们发现，“静息”渗出物 中性粒细胞能够分泌的I1-8比 “静息”的外周血中性粒细胞。当外周血 刺激中性粒细胞，诱导合成I1-8和I1-8 储存在与膜相关的隔室中，该隔室易于移动和 秘而不宣。渗出的中性粒细胞还会产生I1-6和肿瘤坏死因子-α。研究 慢性肉芽肿性疾病患者的介质显示正常 在这些患者中积聚。相比之下，患有这种疾病的患者 高免疫球蛋白E-反复感染(HIE)综合征约有10- Fold增加了水疱液中肿瘤坏死因子-α的积聚。这个 升高的肿瘤坏死因子-α仅限于局部炎症反应 因为在相关研究中，其中一种脂类A组分的制备 给正常志愿者静脉注射大肠杆菌内毒素 HIE组和HIE组大鼠血清中肿瘤坏死因子-α、I1-8和I1-6水平正常升高。 观察HIE受试者的循环情况。肿瘤坏死因子-`的异常调节 局部炎症部位的变化可能在 新生儿缺氧缺血性脑病感染后并发症的发病机制 肺炎后的支气管扩张和支气管胸膜瘘形成。 在相关研究中，静脉注射内毒素给正常人 受试者和中介物产生的动力学在 受试者的血清。I1-8和肿瘤坏死因子-α的升高存在时间相关性 伴随着反应的中性粒细胞减少和发热阶段；增加的 可溶性肿瘤坏死因子-α受体与循环总肿瘤坏死因子-α增加平行 阿尔法。I1-6和G-CSF升高及GM-CSF小幅升高 与中性粒细胞增多和乳铁蛋白升高相关 在静脉注射内毒素之后。血浆I1-1、I1-2和I1-4的变化 静脉注射内毒素后均未检出。

The kinetics of the appearance of cytokines and mediators of inflammation was determined in normal subjects and in selected patients with abnormal host defense. For this study a model of inflammation in the skin was employed using a blister device. Previously we showed that in normal subjects C5a and LTB4 appeared within 3 h of raising blisters, I1-8 and I1-6 appeared from 8 through 24 h and IL1-B, GM-CSF and TNF-alpha appeared from 12 to 24 h. Recently we have shown that "resting" exudate neutrophils are capable of secreting about ten times more I1-8 than "resting" peripheral blood neutrophils. When peripheral blood neutrophils are stimulated, synthesis of I1-8 is induced and I1-8 is stored in a membrane associated compartment that is readily mobilized and secreted. Exudate neutrophils also produce I1-6 and TNF-alpha. Studies in patients with chronic granulomatous disease revealed normal mediator accumulation in these patients. In contrast, patients with the hyperimmunoglobulin E-recurrent infection (HIE) syndrome had about ten- fold increased TNF-alpha accumulation in the blister fluid. The increased TNF-alpha was restricted to the local inflammatory response since in related studies, in which a preparation of the lipid A component of E. coli endotoxin was administered intravenously to normal volunteers and HIE subjects, normal increases in TNF-alpha, I1-8 and I1-6 in the circulation in HIE subjects was observed. Abnormal regulation of TNF-` at local inflammatory sites may have important implications in the pathogenesis of the post infectious complications seen in HIE such as bronchiectasis and bronchopleural fistula formation following pneumonia. In related studies, intravenous endotoxin was administered to normal volunteers and the kinetics of mediator production was followed in the subjects' sera. Increased I1-8 and TNF-alpha was temporally associated with the neutropenic and febrile phases of the response; increased soluble TNF-alpha receptor paralled increased total circulating TNF- alpha. Increases in I1-6 and G-CSF and small increases in GM-CSF correlated with the neutrophilia and increased lactoferrin observed following intravenous endotoxin. Changes in plasma I1-1, I1-2 and I1-4 were not detected following intravenous endotoxin.