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

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.

Keywords: autoimmunity; autoinflammatory disease; cytokine receptors; cytokines; fibroblasts.

Graphical abstract

Figure 1.

Putative pathway of IL-11 signalling leading to fibrosis. IL-11 activates its putative receptor in association with the ubiquitous gp130 receptor initiating a signalling cascade that appears ERK-dependent.This results in phosphorylation of LKB and leads to loss of AMPK and subsequent mTOR activation ultimatley leading to Eife4, which initiates cap-dependant translation of proteins, specifically collagens, and other ECM proteins that endow the cell with a myofibroblast phenotype that leads to fibrosis. Unknowns include the precise role of Eife4 in specificity to collagen proteins and how universal this response is.