Abeywardena Mahinda Y, Leifert Wayne R, Warnes Kirsty E, Varghese Jose N, Head Richard J
CSIRO Human Nutrition, Kintore Avenue, Adelaide, South Australia 5000, Australia.
Curr Pharm Des. 2009;15(15):1809-21. doi: 10.2174/138161209788186290.
Interleukin-6 (IL-6) is a multifunctional pro-inflammatory cytokine that is tightly regulated and expressed at low levels in healthy individuals. Increased IL-6 expression has been associated with a variety of diseases, including inflammatory conditions such as atherosclerosis and cardiovascular disease (obesity, myocardial infarction and type II diabetes). Cytokines including IL-6 and tumour necrosis factor alpha as well as acute phase proteins such as C-reactive protein (CRP) and fibrinogen are key biochemical risk factors for the development of these disease conditions. IL-6 is the key cytokine responsible for the stimulus of synthesis and secretion of CRP. IL-6 activates cell surface signalling via the assembly of IL-6, the IL-6 receptor (IL-6R) and the signalling receptor gp130. Assembly of the (hexameric) signalling complex of IL-6, IL-6R and gp130 occurs in a sequential manner and therefore this signalling complex lends itself to several potential sites for drug targeting. This review discusses some of the mechanisms of IL-6 signalling on various aspects of cardiovascular biology as well as some recent developments in drug targeting of this complex.
白细胞介素-6（IL-6）是一种多功能促炎细胞因子，在健康个体中受到严格调控且表达水平较低。IL-6表达增加与多种疾病相关，包括动脉粥样硬化和心血管疾病（肥胖、心肌梗死和II型糖尿病）等炎症性疾病。包括IL-6和肿瘤坏死因子α在内的细胞因子以及C反应蛋白（CRP）和纤维蛋白原等急性期蛋白是这些疾病发生发展的关键生化危险因素。IL-6是刺激CRP合成和分泌的关键细胞因子。IL-6通过IL-6、IL-6受体（IL-6R）和信号受体gp130的组装激活细胞表面信号传导。IL-6、IL-6R和gp130的（六聚体）信号复合物以顺序方式组装，因此该信号复合物有几个潜在的药物作用靶点。本文综述了IL-6信号传导在心血管生物学各个方面的一些机制以及针对该复合物的药物研发的一些最新进展。
