Interleukin 11 (IL11) is an elusive member of the IL6 family of cytokines. While initially thought to be a haematopoietic and cytoprotective factor, more recent data show instead that IL11 is redundant for haematopoiesis and toxic. In this review, the reasons that led to the original misunderstandings of IL11 biology, which are now understandable, are explained with particular attention on the use of recombinant human IL11 in mice and humans. Following tissue injury, as part of an evolutionary ancient homeostatic response, IL11 is secreted from damaged mammalian cells to signal via JAK/STAT3, ERK/P90RSK, LKB1/mTOR and GSK3β/SNAI1 in autocrine and paracrine. This activates a program of mesenchymal transition of epithelial, stromal, and endothelial cells to cause inflammation, fibrosis, and stalled endogenous tissue repair, leading to organ failure. The role of IL11 signalling in cell- and organ-specific pathobiology is described, the large unknowns about IL11 biology are discussed and the promise of targeting IL11 signalling as a therapeutic approach is reviewed.

中文翻译：

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了解白细胞介素 11 作为疾病基因和治疗靶点

白细胞介素 11 (IL11) 是细胞因子 IL6 家族中难以捉摸的成员。虽然最初认为 IL11 是一种造血和细胞保护因子，但最近的数据表明，IL11 对于造血作用是多余的，并且具有毒性。在这篇综述中，解释了导致对 IL11 生物学的最初误解的原因，这些误解现在已经可以理解，并特别关注重组人 IL11 在小鼠和人类中的使用。组织损伤后，作为进化的古老稳态反应的一部分，IL11 从受损的哺乳动物细胞中分泌，通过 JAK/STAT3、ERK/P90RSK、LKB1/mTOR 和 GSK3β/SNAI1 在自分泌和旁分泌中发出信号。这会激活上皮细胞、基质细胞和内皮细胞的间质转化程序，引起炎症、纤维化和内源性组织修复停滞，从而导致器官衰竭。描述了 IL11 信号传导在细胞和器官特异性病理学中的作用，讨论了有关 IL11 生物学的大量未知因素，并回顾了靶向 IL11 信号传导作为治疗方法的前景。