Exploring valrubicin’s effect on Propionibacterium acnes-induced skin inflammation in vitro and in vivo

Abstract

Acne is a common skin disease involving colonization with <em>Propionibacterium</em> <em>acnes</em> (<em>P</em>. <em>acnes</em>), hyperproliferation of the follicular epithelium and inflammatory events. Valrubicin is a second-generation anthracycline, non-toxic upon contact, and available in a topical formulation. Valrubicin’s predecessor doxorubicin possesses antibacterial effects and previously we demonstrated that valrubicin inhibits keratinocyte proliferation and skin inflammation suggesting beneficial topical treatment of acne with valrubicin. This study aims to investigate valrubicin’s possible use in acne treatment by testing valrubicin’s antibacterial effects against <em>P</em>. <em>acnes</em> and <em>P.</em> <em>acnes</em>-induced skin inflammation <em>in</em> <em>vitro</em> and <em>in</em> <em>vivo</em>. Valrubicin was demonstrated not to possess antibacterial effects against <em>P.</em> <em>acnes</em>. Additionally, valrubicin was demonstrated not to reduce mRNA and protein expression levels of the inflammatory markers interleukin (IL)-1β, IL-8, and tumor necrosis factor (TNF)-α <em>in</em> <em>vitro</em> in human keratinocytes co-cultured with <em>P</em>. <em>acnes</em>. Moreover, <em>in</em> <em>vivo</em>, valrubicin, applied both topically and intra-dermally, was not able to reduce signs of inflammation in mouse ears intra-dermally injected with <em>P</em>. <em>acnes</em>. Taken together, this study does not support beneficial antibacterial and anti inflammatory effects of topical valrubicin treatment of acne.