胸腺五肽的稳定类似物。3. 酮亚甲基假肽的抗关节炎特性评估。

Stabilized analogs of thymopentin. 3. Evaluation of ketomethylene pseudopeptides for antiarthritic properties.

作者信息

Smith R L, Dousman L, Waud W R, DeGraw J I

机构信息

Orthopaedic Research Laboratory, Stanford University Medical Center, California 94305-5341, USA.

出版信息

J Med Chem. 1997 Jul 18;40(15):2407-11. doi: 10.1021/jm950805v.

DOI:10.1021/jm950805v

PMID:9240355

Abstract

This study analyzed the role of ketomethylene pseudopeptides of thymopentin as potential agents for the treatment of arthritis. The analogs were tested in vivo using assessment of inflammation and antibody production in the mouse type II collagen arthritis model and the rat adjuvant arthritis model. The compounds were also tested for immune-potentiating activity in vitro using induction of the lymphocyte marker, Thy-1.2, in mouse spleen cells and stimulation of T-cell proliferation. The results show that certain of the compounds exhibit disease-remitting properties for arthritis as evidenced by reduction of paw swelling in the mouse and rat models and decreased incidence of disease in the mouse model. The active compounds were dose specific and represented a range in efficacy. In spite of effects on arthritis, type II collagen antibody levels were not altered in the mouse model. Selected compounds also exhibited immune potentiating properties as evidenced by induction of Thy-1.2 expression and stimulation of T-cell proliferation. The absence of effect of the compounds on type II collagen antibody production suggests that the antiarthritic activity of the effective compounds results from alteration of cell-mediated immunity.

摘要

本研究分析了胸腺五肽的酮亚甲基假肽作为治疗关节炎潜在药物的作用。使用小鼠II型胶原性关节炎模型和大鼠佐剂性关节炎模型中的炎症评估和抗体产生情况，在体内对这些类似物进行了测试。还使用小鼠脾细胞中淋巴细胞标志物Thy-1.2的诱导以及T细胞增殖的刺激，在体外对这些化合物的免疫增强活性进行了测试。结果表明，某些化合物表现出缓解关节炎的特性，这在小鼠和大鼠模型中爪肿胀减轻以及小鼠模型中疾病发病率降低中得到了证明。活性化合物具有剂量特异性，且疗效存在一定范围。尽管对关节炎有影响，但在小鼠模型中II型胶原抗体水平并未改变。所选化合物还表现出免疫增强特性，这在Thy-1.2表达的诱导和T细胞增殖的刺激中得到了证明。这些化合物对II型胶原抗体产生没有影响，表明有效化合物的抗关节炎活性是由细胞介导的免疫改变引起的。