LYME DISEASE--DEVELOPMENT OF SKIN LESIONS AND ARTHRITIS

老年伴随着能力和攀登倾向的变化。 一种炎症反应。人们不太可能发烧，而 年龄较大的小鼠对致热性更敏感。另一方面，某些人 炎症性疾病，如关节炎，在老年人中更容易发生。 衰老过程中炎性反应改变的机制尚不清楚。 明白了。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。-，在小鼠中将是 调查过了。急性炎症会在皮肤和皮肤中诱发 后爪注射不同剂量的炎性物质和 可能是内源性炎症介质。分布中的变化 中性粒细胞、血清蛋白和红细胞的使用将紧随其后 放射性标记示踪剂。革兰氏阴性细菌内毒素 (脂多糖；脂多糖)将被用作一种外源性燃素。 白介素1，2和6，以及肿瘤坏死因子，组胺， 前列腺素和白三烯将被调查它们是否有能力 在不同年龄的小鼠中诱导炎症反应。组织学 将对具有代表性的病变进行研究。反之， 内毒素或细菌刺激(枯草杆菌)诱导的能力 皮肤中的炎症介质将在不同类型的小鼠身上进行研究 年龄。第二，炎症介质之间的协同作用 将使用两个或更多内源性介体的次优剂量来寻求 注射到兔皮中。一旦确定了有效组合， 它们将在小鼠模型中用不同的小鼠进行研究 年龄，--，.第三，组胺、中性粒细胞和花生四烯酸的作用 在发展炎症反应方面的衍生物将被寻求 用这些介体的抑制物对动物进行预处理。三、分析了 数据可能揭示内源性介质在体内的作用顺序。第四, 通过自然发生来调节炎症反应 白介素1抑制剂将被研究。一种这样的抑制因素是 来源于B细胞系的肿瘤细胞。这一抑制因素将是 纯化，体外表征，并评估其抑制能力 不同年龄云母体内炎症变化。

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.