Interleukin-36? is elevated in diffuse systemic sclerosis and may potentiate fibrosis

Systemic sclerosis (SSc) is an autoimmune prototypical connective tissues disease that results in alterations in vasculature, inflammation and fibrosis of the skin. Interleukin-1 family cytokines has been implicated in the disease including IL-1. IL-36 alpha is an IL-1 family member that is clearly implicated in psoriatic skin disease but its role in systemic sclerosis disease is not clear. The aim of this work is to evaluate the levels and role of IL-36 alpha in systemic sclerosis. Early diffuse SSc patients sera was isolated along with healthy controls and IL-36 levels quantified by ELISA. In vitro analysis was also undertaken with primary dermal fibroblasts with recombinant IL36 alpha and keratinocyte cells were also incubated with IL-36 alpha. Cytokines were measured by ELISA. Serum IL-36 was significantly elevated compared to healthy controls. Elevated neutrophil elastase was also elevated in the matched sera. IL-36 was not directly pro-fibrotic in dermal fibroblasts but did induce pro-inflammatory cytokines that were dependant on the MAPK pathway for their release. IL-36 alpha also led to release of CCL20 and CCL2 in keratinocytes which may potentiate fibrosis. IL-36 alpha is elevated in SSc serum and whilst not directly pro-fibrotic it may through keratinocytes, potentiate fibrosis through keratinocyte-immune fibroblast cross-talk.

Automated summary

IL-36α levels are elevated in systemic sclerosis serum and, although it is not directly pro-fibrotic, it may potentiate fibrosis through keratinocyte-immune fibroblast cross-talk.