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Bonnekoh H, Vera C, Abad-Perez A, et al. Topical inflammasome inhibition with disulfiram prevents irritant contact dermatitis. Clin Transl Allergy. 2021;11(5):e12045doi: 10.1002/clt2.12045.
Bonnekoh, H., Vera, C., Abad-Perez, A., Radetzki, S., Neuenschwander, M., Specker, E., Mahnke, N. A., Frischbutter, S., Latz, E., Nazaré, M., Kries, J. V., Maurer, M., Scheffel, J., & Krause, K. (2021). Topical inflammasome inhibition with disulfiram prevents irritant contact dermatitis. Clinical and translational allergy, 11(5), e12045. https://doi.org/10.1002/clt2.12045
Bonnekoh, Hanna, et al. "Topical inflammasome inhibition with disulfiram prevents irritant contact dermatitis." Clinical and translational allergy vol. 11,5 (2021): e12045. doi: https://doi.org/10.1002/clt2.12045
Bonnekoh H, Vera C, Abad-Perez A, Radetzki S, Neuenschwander M, Specker E, Mahnke NA, Frischbutter S, Latz E, Nazaré M, Kries JV, Maurer M, Scheffel J, Krause K. Topical inflammasome inhibition with disulfiram prevents irritant contact dermatitis. Clin Transl Allergy. 2021 Jul 22;11(5):e12045. doi: 10.1002/clt2.12045. eCollection 2021 Jul. PMID: 34322217; PMCID: PMC8297992.
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Clin Transl Allergy. 2021 Jul 22;11(5):e12045. doi: 10.1002/clt2.12045. eCollection 2021 Jul.

Topical inflammasome inhibition with disulfiram prevents irritant contact dermatitis.

Clinical and translational allergy

Hanna Bonnekoh, Carolina Vera, Angela Abad-Perez, Silke Radetzki, Martin Neuenschwander, Edgar Specker, Niklas Amadeus Mahnke, Stefan Frischbutter, Eicke Latz, Marc Nazaré, Jens V Kries, Marcus Maurer, Jörg Scheffel, Karoline Krause

Affiliations

  1. Dermatological Allergology, Allergie-Centrum-Charité, Department of Dermatology, Venereology and Allergology Charité - Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health Berlin Germany.
  2. Autoinflammation Reference Center Charité (ARC2) Charité - Universitätsmedizin Berlin Berlin Germany.
  3. Department of Chemical Biology Leibniz-Forschungsinstitut für Molekulare Pharmakologie (FMP) Berlin Germany.
  4. Institute of Innate Immunity University of Bonn Bonn Germany.
  5. German Center of Neurodegenerative Diseases (DZNE) University of Bonn Bonn Germany.

PMID: 34322217 PMCID: PMC8297992 DOI: 10.1002/clt2.12045

Abstract

BACKGROUND: The pathogenesis of contact dermatitis, a common inflammatory skin disease with limited treatment options, is held to be driven by inflammasome activation induced by allergens and irritants. We here aim to identify inflammasome-targeting treatment strategies for irritant contact dermatitis.

METHODS: A high content screen with 41,184 small molecules was performed using fluorescent Apoptosis associated speck-like protein containing a CARD (ASC) speck formation as a readout for inflammasome activation. Hit compounds were validated for inhibition of interleukin (IL)-1β secretion. Of these, the approved thiuramdisulfide derivative disulfiram was selected and tested in a patch test model of irritant contact dermatitis in 25 healthy volunteers. Topical application of disulfiram, mometasone or vehicle was followed by application of sodiumdodecylsulfate (SDS) for 24 h each. Eczema induction was quantified by mexameter and laser speckle imaging. Corneocyte sampling of lesional skin was performed to assess inflammasome-mediated cytokines IL-1β and IL-18.

RESULTS: Disulfiram induced a dose-dependent inhibition of ASC speck formation and IL-1β release in cellular assays in vitro. In vivo, treatment with disulfiram, but not with vehicle and less mometasone, inhibited SDS-induced eczema. This was demonstrated by significantly lower erythema and total perfusion values assessed by mexameter and laser speckle imaging for disulfiram compared to vehicle (

CONCLUSION: We show that disulfiram is a dose-dependent inhibitor of inflammasome pathway activation in vitro and inhibitor of SDS-induced eczema in vivo. Topical application of disulfiram represents a potential treatment option for irritant contact dermatitis.

© 2021 The Authors. Clinical and Translational Allergy published by John Wiley & Sons Ltd on behalf of European Academy of Allergy and Clinical Immunology.

Keywords: autoinflammation; contact dermatitis; disulfiram; inflammasome; interleukin‐18

Conflict of interest statement

Carolina Vera, Angela Abad‐Perez, Silke Radetzki, Martin Neuenschwander, Edgar Specker, Marc Nazaré, Jens v. Kries, Niklas Amadeus Mahnke, Jörg Scheffel and Stefan Frischbutter have no conflict of int

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