Development of the method in treatment of Rheumatoid Arthritis (RA) with heat-shock protein, chaperon

目的：探讨静脉注射联苯双酯（BiP）对类风湿性关节炎（SCID）小鼠滑膜移植物滑膜炎特征的影响。方法：将类风湿关节炎患者的滑膜移植到严重联合免疫缺陷（SCID）小鼠皮下。给予静脉内BiP或人血清白蛋白（HSA），并通过以下方式评估其对滑膜炎的影响：比较外植体的重量、组织学外观、共刺激分子CD 86和HLA-DR的免疫组织学存在以及人IL-4、IL-10和IL-6的循环水平。结果：BiP对类风湿性滑膜炎有明显的抑制作用。Rooney和Koizumi技术的炎症组织学评分均降低。这种抑制被BiP处理的外植体的重量减少所抵消（BiP与HSA处理;分别为0.30± 0.09 g与0.37± 0.11 g）。CD 86和HLA-DR表达减少。人IL-6的循环水平降低至背景水平。当在BiP注射之前向小鼠施用人抗IL-10单克隆抗体时，BiP对外植体的重量减轻作用显著逆转。结论：BiP能够逆转类风湿性滑膜炎的组织学和免疫组织学特征以及携带类风湿性外植体的SCID小鼠中的循环人IL-6水平，并表明BiP应作为RA的治疗剂进行试验。

Objective: to investigate the effect of intravenous BiP on the features of synovitis in rheumatoid synovial explants carried by SCID mice. Methods: Synovial membranes from patients with rheumatoid arthritis were transplanted subcutaneously into severe combined immunodeficient (SCID) mice. Intravenous BiP or human serum albumin (HSA) were administered and their effects on synovitis assessed by: comparing the weight of the explants, the histological appearance; the immunohistological presence of the co-stimulatory molecules CD86 and HLA-DR, and the circulating levels of human IL-4, IL-10 and IL-6. Results: BiP had significant suppressive effects on rheumatoid synovitis. There was reduction in the histological scoring of inflammation both by the Rooney and the Koizumi techniques. This suppression was paralleled by a decrease in the weight of the BiP-treated explants (BiP versus HSA treatment; 0.30±0.09g versus 0.37±0.11g, respectively). The expression of CD86 and HLA-DR was reduced. The circulating level of human IL-6 was reduced to background levels. When a human anti-IL-10 monoclonal antibody was administered to the mice prior to BiP injection, there was a significant reversal of the weight reducing effect of BiP on the explants. Conclusion: BiP is able to reverse histological and immunohistological features of rheumatoid synovitis as well as circulating human IL-6 levels in SCID mice bearing rheumatoid explants and suggests that BiP should be trialed as a therapeutic agent in RA.