Glant T T, Mikecz K, Bartlett R R, Deák F, Thonar E J, Williams J M, Mattar T, Kuettner K E, Schleyerbach R
Department of Biochemistry, Rush-Presbyterian-St.-Luke's Medical Center, Chicago, IL 60612.
Immunopharmacology. 1992 Mar-Apr;23(2):105-16. doi: 10.1016/0162-3109(92)90034-a.
Proteoglycan-induced arthritis is a mouse model displaying many similarities to human rheumatoid arthritis and ankylosing spondylitis which has been documented by clinical and histopathological studies. The development of the disease in genetically susceptible BALB/c mice is dependent upon the expression of both cell-mediated and humoral immunity to host mouse cartilage proteoglycan. Since both development and regression of acute inflammatory processes in joints correlate directly with the serum antibody level to mouse cartilage proteoglycan, it is believed that these autoreactive antibodies may play a key role in the pathological mechanism of proteoglycan-induced arthritis. The treatment of arthritic animals with an immunomodulating agent (leflunomide) suppressed acute inflammatory events, protected animals from new inflammatory episodes or acute exacerbations in chronically inflamed joints and blocked pathological processes in arthritic joints, which otherwise led to progressive deformities, ankylosis and the loss of articular cartilage. We conclude that the suppressive effect of leflunomide (HWA 486) in proteoglycan-induced arthritis primarily is due to the suppression of autoantibody formation and that the drug may be a potential agent in human therapy as well. Further, we feel that this novel model of murine polyarthritis will extend further the pharmacological repertoire necessary to discover innovative antirheumatic drugs.
蛋白聚糖诱导的关节炎是一种小鼠模型，临床和组织病理学研究已证明其与人类类风湿性关节炎和强直性脊柱炎有许多相似之处。在基因易感的BALB/c小鼠中，该疾病的发展取决于对宿主小鼠软骨蛋白聚糖的细胞介导免疫和体液免疫的表达。由于关节中急性炎症过程的发展和消退都与针对小鼠软骨蛋白聚糖的血清抗体水平直接相关，因此认为这些自身反应性抗体可能在蛋白聚糖诱导的关节炎的病理机制中起关键作用。用免疫调节剂（来氟米特）治疗关节炎动物可抑制急性炎症事件，保护动物免受新的炎症发作或慢性炎症关节中的急性加重，并阻断关节炎关节中的病理过程，否则这些过程会导致进行性畸形、关节强直和关节软骨丧失。我们得出结论，来氟米特（HWA 486）在蛋白聚糖诱导的关节炎中的抑制作用主要是由于自身抗体形成的抑制，并且该药物也可能是人类治疗中的一种潜在药物。此外，我们认为这种新型的小鼠多关节炎模型将进一步扩展发现创新抗风湿药物所需的药理学范围。
