Rosenthale M E, Capetola R J
Fed Proc. 1982 Jul;41(9):2577-82.
Adjuvant arthritis is an experimental immunopathy that is thought to share many features of human rheumatoid arthritis and, as such, is one of the most widely used models for studying the anti-inflammatory properties of compounds. Adjuvant arthritis can be induced in the rat by the injection of various bacterial cell walls or their components; however, the exact immunogen remains unknown. Recently, an autoantibody response to type II collagen was described not only in the collagen-induced arthritic model but in the adjuvant-induced disease as well. This response thus suggests that shared antigenic determinants exist between type II collagen and the responsible immunogen in the bacterial cell wall components. The contribution of the T lymphocyte to the pathogenesis of adjuvant arthritis is well known. It has now been shown that under specific conditions, adjuvant arthritis can be either enhanced or suppressed with pharmacologic or surgical manipulation, thus suggesting the heterogenicity of T lymphocytes capable of influencing the course of the disease. Levamisole was shown to reverse the augmentation of adjuvant disease seen after adult thymectomy, which suggests that levamisole can restore an aberrant immune response. Monoclonal antibodies are now being developed to evaluate T cell subsets in the rat. The use of these antibodies to study or selectively deplete lymphocyte subpopulations in this disease model promises to reveal immunologic characteristics that may lead to the development of new classes of immunoregulant drugs. Finally, the adjuvant rat has been found useful as a pain model capable of detecting the analgesic properties of both central and the newer peripheral analgesics. The above studies further corroborate the similarities between the immunopathological and hyperalgesic features of human rheumatoid arthritis and adjuvant disease. Recently developed immunologic technology may allow a new look at an old model and may result in the ability to evaluate new classes of immunoregulating agents.
佐剂性关节炎是一种实验性免疫病,被认为与人类类风湿性关节炎有许多共同特征,因此是研究化合物抗炎特性时使用最广泛的模型之一。通过注射各种细菌细胞壁或其成分可在大鼠中诱发佐剂性关节炎;然而,确切的免疫原仍不清楚。最近,不仅在胶原诱导的关节炎模型中,而且在佐剂诱导的疾病中也描述了对II型胶原的自身抗体反应。因此,这种反应表明II型胶原与细菌细胞壁成分中的致病免疫原之间存在共同的抗原决定簇。T淋巴细胞在佐剂性关节炎发病机制中的作用是众所周知的。现已表明,在特定条件下,通过药理或手术操作可增强或抑制佐剂性关节炎,这表明能够影响疾病进程的T淋巴细胞具有异质性。左旋咪唑被证明可逆转成年胸腺切除后出现的佐剂病加剧现象,这表明左旋咪唑可恢复异常的免疫反应。目前正在研制单克隆抗体以评估大鼠的T细胞亚群。在这种疾病模型中使用这些抗体来研究或选择性清除淋巴细胞亚群有望揭示可能导致新型免疫调节药物开发的免疫学特征。最后,已发现佐剂大鼠作为一种疼痛模型可用于检测中枢和新型外周镇痛药的镇痛特性。上述研究进一步证实了人类类风湿性关节炎和佐剂病在免疫病理学和痛觉过敏特征方面的相似性。最近开发的免疫技术可能会使人们重新审视这个旧模型,并可能使评估新型免疫调节药物成为可能。