Mechanistic Insight into the Activity of a Sulfone Compound Dapsone on Propionibacterium (Newly Reclassified as Cutibacterium) Acnes–Mediated Cytokine Production

Abstract

Acne remains as the most common skin disease in the US even despite multiple approved topical and systemic medications available. These treatments available over the counter and by prescription can be classified based on comedolytic, antibacterial, and anti‐inflammatory activities and are often used in combination. Therefore, understanding of the mechanism of action is critical to achieving the best clinical outcome and synergy. One of the newer acne medications with historical data suggesting both antibacterial and anti‐inflammatory activity is dapsone. In order to gain mechanistic insight into the anti‐inflammatory activity of dapsone in Propionibacterium (a former genus name recently reclassified as "Cutibacterium") (P. acnes)–driven inflammation we used two human in vitro models: primary human neonatal epidermal keratinocytes and human monocytes (THP‐1). We demonstrate that dapsone suppresses production of specific cytokine signatures interleukin (IL)1α and IL8 in human epidermal keratinocytes and IL1β, IL6, IL8, and tumor necrosis factor‐α in THP‐1 cells in response to P. acnes. Using THP‐1 cell in vitro model we show that IL1β and CASP‐1 are regulated by dapsone independently of NFκB activity at transcriptional and post transcriptional levels respectively.

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