The IL-1 family of cytokines. Do they have a role in scleroderma fibrosis?

Abstract

Systemic sclerosis is a profibrotic autoimmune disease mediated by the dysregulation in collagen synthesis, leading to the increased deposition of collagens, primarily type I and III, and the deposition of other extracellular matrix proteins in the skin and internal organs, in a mechanism that is thought to be an over active wound healing process. These patients experience significant morbidity and the mortality rate in this disease is high. Indeed, scleroderma is the most deadly of diseases in the autoimmune spectrum. Recent evidence has placed the assembly and chronic activation of the inflammasome as a central driver of fibrosis. Once assembled, the inflammasome is a large protein complex that regulates the release of IL-1, IL-18, and IL-33, which are thought to play a role in the fibrotic response. IL-36 also belongs to the IL-1 family of cytokines and is a new comer to this field of research. Recent analyses of the IL-1 family of cytokines have demonstrated that many of them play a role in skin inflammation and fibrosis and their corresponding antagonists (IL-1RA and IL-36RA) can abrogate this pathology. Understanding how these cytokines are regulated and how they contribute to fibrosis will be important to understanding this pathology and may shed light in new areas for therapeutic development.

Keywords: Fibrosis; IL-1; IL-18; IL-33; IL-36; Systemic sclerosis.