Simms Robert W, Korn Joseph H
Rheumatology Section, Department of Medicine, Boston University School of Medicine, Massachusetts, USA.
Curr Opin Rheumatol. 2002 Nov;14(6):717-22. doi: 10.1097/00002281-200211000-00015.
The hallmark of scleroderma is cutaneous and visceral fibrosis characterized and by increased biosynthesis of multiple matrix proteins by interstitial fibroblasts. Studies over recent years have delineated pathways involved in promoting matrix synthesis and elucidated the molecular pathways of regulation. Central to the regulation of fibrosis are extracellular mediators, called cytokines, which are elaborated by a variety of cells, including those in the immune system, vascular cells, and fibroblasts themselves. The concept that inhibiting or promoting the action of these naturally occurring profibrotic or antifibrotic molecules, respectively, is a rational therapeutic approach to treating scleroderma and other fibrotic diseases finds support in animal studies and anticytokine therapy conducted in relation to rheumatoid arthritis and other disorders. This review looks at cytokines known or thought to play a role in scleroderma and/or other fibrotic states and at potential therapy directed at these mediators. Potential targets for therapy include transforming growth factor beta (TGF-beta), connective tissue growth factor (CTGF), IL-4, IL-13, MCP-1, and endothelin, among others.
硬皮病的标志是皮肤和内脏纤维化，其特征是间质成纤维细胞合成多种基质蛋白的生物合成增加。近年来的研究已经阐明了促进基质合成的相关途径，并阐明了调控的分子途径。纤维化调控的核心是细胞外介质，即细胞因子，它们由多种细胞产生，包括免疫系统细胞、血管细胞和成纤维细胞本身。分别抑制或促进这些天然存在的促纤维化或抗纤维化分子的作用是治疗硬皮病和其他纤维化疾病的合理治疗方法，这一概念在动物研究以及针对类风湿关节炎和其他疾病进行的抗细胞因子治疗中得到了支持。本综述探讨了已知或被认为在硬皮病和/或其他纤维化状态中起作用的细胞因子，以及针对这些介质的潜在治疗方法。潜在的治疗靶点包括转化生长因子β（TGF-β）、结缔组织生长因子（CTGF）、IL-4、IL-13、MCP-1和内皮素等。
