Bendele A, McComb J, Gould T, McAbee T, Sennello G, Chlipala E, Guy M
BoulderPATH, Inc., Boulder, Colorado 80309, USA.
Toxicol Pathol. 1999 Jan-Feb;27(1):134-42. doi: 10.1177/019262339902700125.
Animal models of arthritis are used to evaluate potential antiarthritis drugs for clinical use. Therefore capacity of the model to predict efficacy in human disease is one of the most important criteria in model selection. Animal models of rheumatoid arthritis (RA) with a proven track record of predictability include rat adjuvant arthritis, rat type II collagen arthritis, mouse type II collagen arthritis, and antigen-induced arthritis in several species. Agents currently in clinical use (or trials) that are active in these models include corticosteroids, methotrexate, nonsteroidal anti-inflammatory drugs, cyclosporin A, leflunomide, interleukin-1 receptor antagonist, and soluble tumor necrosis factor receptors. For some of these agents, the models also predict that toxicities seen at higher doses for prolonged periods would preclude dosing in humans at levels that might provide disease-modifying effects. Animal models of osteoarthritis (OA) include mouse and guinea pig spontaneous OA, meniscectomy and ligament transection in guinea pigs, meniscectomy in rabbits, and meniscectomy and cruciate transection in dogs. None of these models have a proven track record of predictability in human disease because there are no agents that have been proven to provide anything other than symptomatic relief in human OA. Efficacy data and features of the various models of RA and OA are discussed with emphasis on their proven relevance to human disease.
关节炎动物模型用于评估潜在的抗关节炎药物以供临床使用。因此，模型预测人类疾病疗效的能力是模型选择中最重要的标准之一。具有可靠预测记录的类风湿性关节炎（RA）动物模型包括大鼠佐剂性关节炎、大鼠II型胶原性关节炎、小鼠II型胶原性关节炎以及多种物种的抗原诱导性关节炎。目前在这些模型中有效的临床使用（或试验中）药物包括皮质类固醇、甲氨蝶呤、非甾体抗炎药、环孢素A、来氟米特、白细胞介素-1受体拮抗剂和可溶性肿瘤坏死因子受体。对于其中一些药物，模型还预测，长期高剂量使用时出现的毒性会使在人体中使用可能产生疾病改善作用的剂量成为禁忌。骨关节炎（OA）动物模型包括小鼠和豚鼠自发性OA、豚鼠半月板切除术和韧带横断术、兔半月板切除术以及犬半月板切除术和十字韧带横断术。这些模型均没有在人类疾病中可靠的预测记录，因为在人类OA中，尚无已被证实能提供除症状缓解之外任何效果的药物。本文讨论了各种RA和OA模型的疗效数据及特点，重点强调了它们与人类疾病已被证实的相关性。
