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Susanne Schiffmann,1,2 Sandra Gunne,1,2 Marina Henke,1 Thomas Ulshöfer,1 Dieter Steinhilber,1 Annette Sethmann,3 Michael J Parnham1 1Fraunhofer Institute for Translational Medicine and Pharmacology (ITMP), Frankfurt am Main, 60596, Germany; 2Pharmazentrum Frankfurt/ZAFES, Department of Clinical Pharmacology, Goethe-University Hospital Frankfurt, Frankfurt am Main, 60590, Germany; 3ICHTHYOL-GESELLSCHAFT Cordes, Hermanni & Co. (GmbH & Co.) KG, Hamburg, 22335, GermanyCorrespondence: Susanne SchiffmannFraunhofer Institute for Translational Medicine and Pharmacology (ITMP), Theodor-Stern-Kai 7, Frankfurt am Main, 60596, GermanyTel +49/69-870025060Fax +49/69-870010000Email susanne.schiffmann@itmp.fraunhofer.deBackground: Sodium bituminosulfonate is derived from naturally occurring sulphur-rich oil shale and is used for the treatment of the inflammatory skin disease rosacea. Major molecular players in the development of rosacea include the release of enzymes that process antimicrobial peptides which, together with reactive oxygen species (ROS) and vascular endothelial growth factor (VEGF), promote pro-inflammatory processes and angiogenesis. The aim of this study was to address the molecular mechanism(s) underlying the therapeutic benefit of the formulation sodium bituminosulfonate dry substance (SBDS), which is indicated for the treatment of skin inflammation, including rosacea.Methods: We investigated whether SBDS regulates the expression of cytokines, the release of the antimicrobial peptide LL-37, calcium mobilization, proteases (matrix metalloproteinase, elastase, kallikrein (KLK)5), VEGF or ROS in primary human neutrophils. In addition, activity assays with 5-lipoxygenase (5-LO) and recombinant human MMP9 and KLK5 were performed.Results: We observed that SBDS reduces the release of the antimicrobial peptide LL-37, calcium, elastase, ROS and VEGF from neutrophils. Moreover, KLK5, the enzyme that converts cathelicidin to LL-37, and 5-LO that pr