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白细胞介素-11 及其在组织纤维化中的重要作用:一个可能的治疗靶点。

Interleukin-11 and its eminent role in tissue fibrosis: a possible therapeutic target.

机构信息

Department of Biosciences, Durham University, Durham, UK.

出版信息

Clin Exp Immunol. 2023 Dec 12;214(2):154-161. doi: 10.1093/cei/uxad108.

Abstract

Interleukin-11 is a cytokine from the IL-6 family of cytokines that includes IL-6 and oncostatin-M. Initially described for its role in platelet generation, it is now appreciated that this cytokine has multiple functions. Recently it has been found that IL-11 is critical in fibrosis in multiple different organ systems and systemically as in the autoimmune disease systemic sclerosis. Animal models of fibrosis have determined that animals with IL-11 receptor deletions have retarded fibrosis and that in wild-type animals IL-11 is found at the organ of fibrosis. Recent evidence suggests that IL-11 may be a master regulator of fibrosis regardless of end target organ. With the development of neutralizing antibodies targeting the cytokine in pre-clinical models this could be a possible therapeutic, in a disease in which no specific therapies exist. This review appraises the evidence of the role of IL-11 in tissue fibrosis, its signalling properties, and therapeutic targeting. The review ends with an appraisal of indications for which IL-11 modulation is targeted.

摘要

白细胞介素-11 是一种细胞因子,属于细胞因子家族中的白细胞介素-6,包括白细胞介素-6 和肿瘤坏死因子-M。最初因其在血小板生成中的作用而被描述,现在人们已经意识到这种细胞因子具有多种功能。最近发现,白细胞介素-11 在多种不同的器官系统和全身性疾病(如自身免疫性疾病系统性硬化症)中的纤维化中起着关键作用。纤维化的动物模型已经确定,白细胞介素-11 受体缺失的动物纤维化进展缓慢,而在野生型动物中,白细胞介素-11 存在于纤维化的器官中。最近的证据表明,白细胞介素-11 可能是纤维化的主要调节因子,而不管其最终靶器官如何。随着针对该细胞因子的中和抗体在临床前模型中的开发,这可能是一种治疗方法,因为目前尚无针对这种疾病的特定治疗方法。本文综述了白细胞介素-11 在组织纤维化中的作用、信号转导特性和治疗靶点的证据。本文最后评估了白细胞介素-11 调节的适应症。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5896/10714194/c4d45ff0a5db/uxad108_fig2.jpg

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