Characterisation of IL‐1 family members in Sweet syndrome highlights the overexpression of IL‐1β and IL‐1R3 as possible therapeutic targets

Abstract

AbstractSweet syndrome (SS) as a prototypic neutrophilic dermatosis (NDs) shares certain clinical and histologic features with monogenic auto‐inflammatory disorders in which interleukin (IL)‐1 cytokine family members play an important role. This has led to the proposal that NDs are polygenic auto‐inflammatory diseases and has fuelled research to further understand the role of IL‐1 family members in the pathogenesis of NDs. The aim of this study was to characterise the expression of the IL‐1 family members IL‐1β, IL‐36γ, IL‐33 and IL‐1R3 (IL‐1RaP) in SS. The expression profile of IL‐1β, IL‐33, IL‐36γ and their common co‐receptor IL‐1R3 was analysed by immunohistochemistry, in situ hybridisation and double immunofluorescence (IF) in healthy control skin (HC) and lesional skin samples of SS. Marked overexpression of IL‐1β in the dermis of SS (p < 0.001), and a non‐significant increase in dermal (p = 0.087) and epidermal (p = 0.345) IL‐36γ expression compared to HC was observed. Significantly increased IL‐1R3 expression within the dermal infiltrate of SS skin samples (p = 0.02) was also observed, whereas no difference in IL‐33 expression was found between SS and HC (p = 0.7139). In situ hybridisation revealed a good correlation between gene expression levels and the above protein expression levels. Double IF identifies neutrophils and macrophages as the predominant sources of IL‐1β. This study shows that IL‐1β produced by macrophages and neutrophils and IL‐1R3 are significantly overexpressed in SS, thereby indicating a potential pathogenic role for this cytokine and receptor in SS.