PATHOGENESIS OF ADJUVANT ARTHRITIS

大鼠的佐剂性关节炎可通过单次注射一种 某些干热杀灭微生物如分枝杆菌的乳剂， 棒状杆菌、链球菌或它们的细胞壁组分，在合适的培养基中， 油性载具 该疾病类似于HLA-B27阳性 脊椎关节病，如赖特综合征，并分享许多 与类风湿性关节炎相似。 这种疾病被认为是 由对抗原的细胞介导的免疫应答引起， 仍然难以捉摸 我们最近的研究结果表明， 病原免疫原来源于宿主，而不是来自 注入的物质。 我们进一步发现， II型胶原蛋白不是诱导或维持这一过程的主要因素。 疾病 这些发现，加上其他考虑，使我们 相信免疫原负责的发病机制， 大鼠的佐剂性关节炎是在大鼠关节内形成的改变的自身物质。 分枝杆菌引起的肉芽肿，并由 蛋白水解酶 长期目标是阐明 这种实验性疾病的发病机制，这是目的， 建议通过三项调查来检验上述假设 独立的方法：1）通过确定慢性关节炎是否可以 在某些免疫刺激条件下， 包含在实验性肉芽肿中，以及2）通过确定是否 对弗氏完全性关节炎的“耐受性”（关于关节炎诱导） 佐剂可以通过用以下油乳剂预处理幼鼠来诱导： 肉芽肿提取物和3）通过确定是否水提取物 炎症组织和/或其分离的成分，例如蛋白聚糖和 连接蛋白，可以诱导抗原特异性的胚细胞转化， 佐剂性关节炎大鼠的淋巴细胞。 拟议的研究 佐剂性关节炎可能会导致更好地了解 人类风湿性疾病的病因机制，它类似。 每个 新的进展，我们的知识的性质和发病机制，这些 疾病代表了扩大我们的诊断和 这可能导致更好的临床管理。

Adjuvant arthritis in the rat can be induced by a single injection of an emulsion of certain dried heat killed microorganisms such as Mycobacteria, Corynebacteria, streptococci, or their cell wall components in a suitable oily vehicle. The disease resembles HLA-B27 positive spondylo-arthropathies such as the Reiter's syndrome and shares many similarities with rheumatoid arthritis. The disease has been believed to arise from a cell-mediated immune response to antigen(s) whose identity remains elusive. Results obtained from our recent studies indicated that the etiologic immunogen(s) is derived from the host rather than that from the injected substances. We have found further that autoimmunity to type II collagen is not a major factor in the induction or maintenance of this disease. These findings, together with other considerations, have led us to the belief that the immunogens responsible for the pathogenesis of adjuvant arthritis in the rat are altered self substances formed in the mycobacteria-induced granuloma and resulting from partial degradation by proteolytic enzymes. With the long term goal of elucidating the pathogenesis of this experimental disease, it is the objective of this proposed investigation to test the above hypothesis through three independent approaches: 1) by determining whether a chronic arthritis can be induced in rats under certain immunostimulatory conditions by substances contained in experimental granuloma and 2) by determining whether "tolerance" (with respect to arthritis induction) to Freund's complete adjuvant can be induced by pretreating young rats with oil emulsions of granuloma extract and 3) by determining whether aqueous extracts of inflammed tissue and/or its isolated constituents, e.g. proteoglycans and link proteins, can induce antigen specific blast transformation of lymphocytes from rats with adjuvant arthritis. The proposed study on adjuvant arthritis may lead to a better understanding of the aetiopathogenesis of human rheumatologic diseases which it resembles. Each new advance in our knowledge on the nature and pathogenesis of these diseases represent a new possibility of enlarging our diagnostic and therapeutic spectrum which may lead to a better clinical management.