Mindrescu C, Thorbecke G J, Klein M J, Vilcek J, Wisniewski H G
New York University School of Medicine, New York 10016, USA.
Arthritis Rheum. 2000 Dec;43(12):2668-77. doi: 10.1002/1529-0131(200012)43:12<2668::AID-ANR6>3.0.CO;2-E.
To examine the effect of recombinant TSG-6 on collagen-induced arthritis (CIA) in DBA/1J mice. TSG-6 is a tumor necrosis factor (TNF)/ interleukin-1 (IL-1)-inducible hyaluronan-binding protein produced by synovial cells and chondrocytes that is present in synovial fluids of patients with rheumatoid arthritis.
To determine the effect of TSG-6 on chronic inflammatory joint disease, we induced CIA in DBA/1J mice by immunization with bovine type II collagen. Animals were treated with 12 intraperitoneal doses of 200 microg of recombinant TSG-6, beginning 3 days before the expected onset of disease symptoms. Progression of arthritis was monitored by determining the disease incidence, arthritis index, and footpad swelling. Levels of IgG1, IgG2a, and IgG2b antibodies against bovine and murine type II collagen and serum concentrations of IL-6 were determined at various time points. Histologic examination of affected joints was performed approximately 20 days after the onset of arthritis.
Treatment with recombinant TSG-6 protein had a potent ameliorative effect, manifested by decreases in the disease incidence, arthritis index, and footpad swelling. Histologic examination of affected joints in TSG-6-treated animals revealed little pannus formation and cartilage erosion, features which were conspicuous in control mice. Animals treated with recombinant TSG-6 developed significantly reduced levels of IgG1, IgG2a, and IgG2b antibodies against bovine and murine type II collagen.
The antiinflammatory effect of the TNF/IL-1-inducible TSG-6 protein in murine CIA suggests a role for this protein as an endogenous regulator of the inflammatory process.
研究重组TSG-6对DBA/1J小鼠胶原诱导性关节炎（CIA）的影响。TSG-6是一种由滑膜细胞和软骨细胞产生的肿瘤坏死因子（TNF）/白细胞介素-1（IL-1）诱导的透明质酸结合蛋白，存在于类风湿性关节炎患者的滑液中。
为确定TSG-6对慢性炎症性关节疾病的影响，我们通过用牛II型胶原免疫诱导DBA/1J小鼠发生CIA。在预期疾病症状出现前3天开始，给动物腹腔注射12次剂量为200微克的重组TSG-6。通过确定疾病发病率、关节炎指数和足垫肿胀来监测关节炎的进展。在不同时间点测定抗牛和鼠II型胶原的IgG1、IgG2a和IgG2b抗体水平以及IL-6的血清浓度。在关节炎发作后约20天对受影响的关节进行组织学检查。
重组TSG-6蛋白治疗具有显著的改善作用，表现为疾病发病率、关节炎指数和足垫肿胀降低。对接受TSG-6治疗的动物的受影响关节进行组织学检查发现，几乎没有血管翳形成和软骨侵蚀，而这些特征在对照小鼠中很明显。接受重组TSG-6治疗的动物产生的抗牛和鼠II型胶原的IgG1、IgG2a和IgG2b抗体水平显著降低。
TNF/IL-1诱导的TSG-6蛋白在小鼠CIA中的抗炎作用表明该蛋白作为炎症过程的内源性调节因子发挥作用。
