Joyce D A, Steer J H, Abraham L J
Department of Pharmacology, University of Western Australia, Nedlands.
Inflamm Res. 1997 Nov;46(11):447-51. doi: 10.1007/s000110050222.
Glucocorticoids suppress many functions in activated monocyte/macrophages, including the release of TNF-alpha. This is likely to contribute to the efficacy of glucocorticoids in some inflammatory diseases, such as rheumatoid arthritis, where TNF-alpha contributes to pathogenesis. Glucocorticoids suppress the activity of reporters which include TNF-alpha promoter regions and modify the activity of NF-kappa B family transcription factors in activated human monocytic cell lines, suggesting effects of glucocorticoids on TNF-alpha gene transcription. In addition, glucocorticoids have been reported to antagonise the enhanced translational efficiency of TNF-alpha mRNA which occurs at least after stimulation of murine monocytic cells. It is likely, therefore, that glucocorticoids act at several points in stimulated monocyte/ macrophages to reduce TNF-alpha secretion. Understanding glucocorticoid control of TNF-alpha secretion may explain some of the variability in response to GC in inflammatory diseases and may reveal means of inducing glucocorticoid-like anti-inflammatory effects in monocyte/macrophages without exposing other tissues to the adverse effects of glucocorticoids.
糖皮质激素可抑制活化的单核细胞/巨噬细胞的多种功能，包括肿瘤坏死因子-α（TNF-α）的释放。这可能有助于糖皮质激素在某些炎症性疾病（如类风湿性关节炎）中发挥疗效，在类风湿性关节炎中TNF-α参与发病机制。糖皮质激素可抑制包含TNF-α启动子区域的报告基因的活性，并改变活化的人单核细胞系中核因子-κB（NF-κB）家族转录因子的活性，提示糖皮质激素对TNF-α基因转录有影响。此外，据报道糖皮质激素可拮抗至少在刺激小鼠单核细胞后出现的TNF-α mRNA翻译效率增强。因此，糖皮质激素可能在刺激的单核细胞/巨噬细胞的多个环节发挥作用，以减少TNF-α的分泌。了解糖皮质激素对TNF-α分泌的调控可能有助于解释炎症性疾病中对糖皮质激素反应的一些变异性，并可能揭示在不使其他组织暴露于糖皮质激素不良反应的情况下，在单核细胞/巨噬细胞中诱导糖皮质激素样抗炎作用的方法。
