LYME DISEASE--DEVELOPMENT OF SKIN LESIONS AND ARTHRITIS

莱姆病——皮肤损伤和关节炎的发展

• 批准号: 3157451
• 负责人: GAIL S HABICHT
• 金额: $ 13.73万
• 依托单位: STATE UNIVERSITY NEW YORK STONY BROOK
• 依托单位国家: 美国
• 财政年份: 1985
• 资助国家: 美国
• 起止时间: 1985-09-23 至 1994-02-28
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3157451
• 关键词: B lymphocyte; Bacillus subtilis; Ixodes; aging; arachidonate; arthritis; blood proteins; borreliosis; erythrocytes; histamine; inflammation; interleukin 1; interleukin 2; interleukin 6; joint disorder; laboratory mouse; laboratory rabbit; lipopolysaccharides; neutrophil; radiotracer; tumor necrosis factor alpha

Old age is accompanied by changes in the capacity and propensity to mount an inflammatory response. People are less likely to become febrile while aged mice are more susceptible to pyrogenicity. On the other hand, certain inflammatory diseases such as arthritis occur more frequently in the aged. The mechanisms of altered inflammatory responses in aging are poorly understood. Thus, the specific aims of the present proposal are fourfold. First, the effects of aging on inflammatory response.-, in mice will be investigated. Acute inflammation will be induced in the skin and in the hind paws by injection of various doses of phlogistic materials and putative endogenous mediators of inflammation. Changes in the distribution of neutrophils serum proteins and erythrocytes will be followed by the use of radioactively labeled tracers. Gram negative bacterial endotoxin (lipopolysaccharide; LPS) will be used as an extrinsic phlogiston. Interleukins 1, 2 and 6, as well as tumor necrosis factor, histamine, prostaglandins and leukotrienes will be investigated for their ability to induce an inflammatory response in mice of different ages. Histological studies of representative lesions will be undertaken. Conversely, the ability of LPS or a bacterial challenge (Bacillus subtilis) to induce inflammatory mediators in skin will be investigated in mice of different ages. Secondly, synergistic interactions between inflammatory mediators will be sought using suboptimal doses of two or more endogenous mediators injected into rabbit skin. once active combinations have been determined, they will be investigated in the mouse models using mice of different age,--,. Thirdly, the roles of histamine, neutrophils and arachidonic acid derivatives in the development of inflammatory responses will be sought by pretreating animals with inhibitors of these mediators. Analysis of the data may reveal an order by which endogenous mediators act in vivo. Fourth, the regulation of the inflammatory response by naturally occurring interleukin 1 inhibitors will be investigated. One such inhibitor is derived from tumor cells of the B cell lineage. This inhibitor will be purified, characterized in vitro and assessed for its ability to inhibit inflammatory changes in vivo in mica-of different ages.

随着年龄的增长， 炎症反应人们不太可能发烧， 老年小鼠更易发生致热原性。 另一方面，某些 炎性疾病如关节炎在老年人中更常见。 衰老过程中炎症反应改变的机制并不清楚， 明白因此，本提案的具体目标有四个方面。 首先，衰老对炎症反应的影响。在小鼠中， 研究了急性炎症将在皮肤和 通过注射不同剂量的致炎物质， 假定的炎症内源性介质。分布的变化 中性粒细胞、血清蛋白和红细胞将随后使用 放射性标记的示踪剂。革兰氏阴性细菌内毒素 （脂多糖; LPS）将用作外源性燃素。 白细胞介素1、2和6，以及肿瘤坏死因子、组胺， 将研究三尖杉酯碱和白三烯的能力， 在不同年龄的小鼠中诱导炎症反应。组织学 将对代表性病变进行研究。反之， LPS或细菌挑战（枯草芽孢杆菌）诱导 皮肤中的炎症介质将在不同的小鼠中进行研究。 年龄其次，炎症介质之间的协同作用 将使用两种或更多种内源性介质的次优剂量来寻求 注射到兔子的皮肤上一旦确定了有效组合， 它们将在小鼠模型中进行研究， 年龄，--，.第三，组胺、中性粒细胞和花生四烯酸的作用 在炎症反应的发展中的衍生物将寻求 用这些介质的抑制剂预处理动物。分析 数据可以揭示内源性介质在体内起作用的顺序。第四、 通过自然发生的炎症反应调节 将研究白细胞介素1抑制剂。一种这样的抑制剂是 来源于B细胞谱系的肿瘤细胞。该抑制剂将 纯化，体外表征并评估其抑制 不同年龄的云母体内炎症变化。