Pargellis Christopher, Regan John
Department of Immunology/Inflammation Chemistry, Boehringer Ingelheim Pharmaceuticals Research and Development Center, 900 Ridgebury Road, Ridgefield, CT 06877, USA.
Curr Opin Investig Drugs. 2003 May;4(5):566-71.
The p38 mitogen-activated protein kinase pathway is involved in a number of cellular processes critical to the development of rheumatoid arthritis. The activation and infiltration of leukocytes as well as the production of inflammatory cytokines are p38-dependent processes. In addition, p38 regulates the differentiation of osteoclasts, which are directly involved in bone loss. Numerous inhibitors of p38 have demonstrated efficacy in animal models of arthritic disease and at least two p38 inhibitors are currently in phase II clinical trials for rheumatoid arthritis. Several other p38 inhibitors are currently undergoing phase I clinical trials.
p38丝裂原活化蛋白激酶通路参与了类风湿关节炎发展过程中许多关键的细胞过程。白细胞的激活与浸润以及炎性细胞因子的产生都是p38依赖的过程。此外，p38调节破骨细胞的分化，而破骨细胞直接参与骨质流失。众多p38抑制剂已在关节炎疾病动物模型中显示出疗效，目前至少有两种p38抑制剂正处于类风湿关节炎的II期临床试验阶段。其他几种p38抑制剂目前正在进行I期临床试验。
