PATHOGENESIS OF ADJUVANT ARTHRITIS

大鼠佐剂性关节炎可通过单次注射An诱导 某些干热杀灭微生物的乳剂，如分枝杆菌， 棒状杆菌、链球菌或它们的细胞壁成分 油污的车辆。这种疾病类似于人类白细胞抗原B27阳性。 脊柱-关节病，如雷特综合征，并有许多共同的 与类风湿性关节炎相似。这种疾病一直被认为是 源于对抗原的细胞免疫反应(S)，其身份是 仍然难以捉摸。我们最近的研究结果表明， 病原学免疫原(S)来自宿主而不是来自宿主 注射的物质。我们进一步发现，自身免疫型 I型胶原蛋白不是诱导或维持这一现象的主要因素 疾病。这些发现，加上其他方面的考虑，使我们 相信免疫原会导致这种疾病的发病 大鼠佐剂性关节炎是由自身物质改变而形成的 分枝杆菌引起的肉芽肿和部分降解 蛋白水解酶。其长期目标是阐明 这种实验性疾病的发病机制，这是本研究的目的 建议的调查通过三个方面来检验上述假设 独立的方法：1)通过确定慢性关节炎是否可以 在一定的免疫刺激条件下由物质诱导大鼠 包含在实验性肉芽肿中，以及2)通过确定 对弗洛因德完全性关节炎的“耐受性”(就关节炎诱导而言) 乳油乳剂可诱导幼鼠产生佐剂 肉芽肿提取物和3)通过确定水提物是否 炎症组织和/或其分离成分，例如蛋白多糖和 连接蛋白，可诱导抗原特异的原始细胞转化 佐剂性关节炎大鼠的淋巴细胞。建议进行的研究 佐剂性关节炎可能会使我们更好地理解 它与人类风湿病的病因病机相似。每个人 我们对这些疾病的本质和发病机制的认识新进展 疾病代表着一种新的可能性，可以扩大我们的诊断和 治疗谱，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.