Omiganan Enhances Imiquimod‐Induced Inflammatory Responses in Skin of Healthy Volunteers

Omiganan (OMN; a synthetic cationic peptide) and imiquimod (IMQ; a TLR7 agonist) have synergistic effects on interferon responses in vitro. The objective of this study was to translate this to a human model for proof‐of‐concept, and to explore the potential of OMN add‐on treatment for viral skin dis...

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Main Authors: Tessa Niemeyer‐van der Kolk, Salma Assil, Thomas P. Buters, Melanie Rijsbergen, Erica S. Klaassen, Gary Feiss, Edwin Florencia, Errol P. Prens, Jacobus Burggraaf, Martijn B.A. vanDoorn, Robert Rissmann, Matthijs Moerland
Format: Article
Language:English
Published: Wiley 2020-05-01
Series:Clinical and Translational Science
Online Access:https://doi.org/10.1111/cts.12741
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spelling doaj-42391760444a4082ab3df6cc9a119ef12020-11-25T02:59:24ZengWileyClinical and Translational Science1752-80541752-80622020-05-0113357357910.1111/cts.12741Omiganan Enhances Imiquimod‐Induced Inflammatory Responses in Skin of Healthy VolunteersTessa Niemeyer‐van der Kolk0Salma Assil1Thomas P. Buters2Melanie Rijsbergen3Erica S. Klaassen4Gary Feiss5Edwin Florencia6Errol P. Prens7Jacobus Burggraaf8Martijn B.A. vanDoorn9Robert Rissmann10Matthijs Moerland11Centre for Human Drug Research Leiden The NetherlandsCentre for Human Drug Research Leiden The NetherlandsCentre for Human Drug Research Leiden The NetherlandsCentre for Human Drug Research Leiden The NetherlandsCentre for Human Drug Research Leiden The NetherlandsCutanea Life Science Wayne Pennsylvania USADepartment of Dermatology, Erasmus Medical Centre Rotterdam The NetherlandsDepartment of Dermatology, Erasmus Medical Centre Rotterdam The NetherlandsCentre for Human Drug Research Leiden The NetherlandsDepartment of Dermatology, Erasmus Medical Centre Rotterdam The NetherlandsCentre for Human Drug Research Leiden The NetherlandsCentre for Human Drug Research Leiden The NetherlandsOmiganan (OMN; a synthetic cationic peptide) and imiquimod (IMQ; a TLR7 agonist) have synergistic effects on interferon responses in vitro. The objective of this study was to translate this to a human model for proof‐of‐concept, and to explore the potential of OMN add‐on treatment for viral skin diseases. Sixteen healthy volunteers received topical IMQ, OMN, or a combination of both for up to 4 days on tape‐stripped skin. Skin inflammation was quantified by laser speckle contrast imaging and 2D photography, and molecular and cellular responses were analyzed in biopsies. IMQ treatment induced an inflammatory response of the skin. Co‐treatment with OMN enhanced this inflammatory response to IMQ, with increases in perfusion (+17.1%; 95% confidence interval (CI) 5.6%–30%; P < 0.01) and erythema (+1.5; 95% CI 0.25%–2.83; P = 0.02). Interferon regulatory factor‐driven and NFκB‐driven responses following TLR7 stimulation were enhanced by OMN (increases in IL‐6, IL‐10, MXA, and IFNɣ), and more immune cell infiltration was observed (in particular CD4+, CD8+, and CD14+ cells). These findings are in line with the earlier mechanistic in vitro data, and support evaluation of imiquimod/OMN combination therapy in human papillomavirus‐induced skin diseases.https://doi.org/10.1111/cts.12741
collection DOAJ
language English
format Article
sources DOAJ
author Tessa Niemeyer‐van der Kolk
Salma Assil
Thomas P. Buters
Melanie Rijsbergen
Erica S. Klaassen
Gary Feiss
Edwin Florencia
Errol P. Prens
Jacobus Burggraaf
Martijn B.A. vanDoorn
Robert Rissmann
Matthijs Moerland
spellingShingle Tessa Niemeyer‐van der Kolk
Salma Assil
Thomas P. Buters
Melanie Rijsbergen
Erica S. Klaassen
Gary Feiss
Edwin Florencia
Errol P. Prens
Jacobus Burggraaf
Martijn B.A. vanDoorn
Robert Rissmann
Matthijs Moerland
Omiganan Enhances Imiquimod‐Induced Inflammatory Responses in Skin of Healthy Volunteers
Clinical and Translational Science
author_facet Tessa Niemeyer‐van der Kolk
Salma Assil
Thomas P. Buters
Melanie Rijsbergen
Erica S. Klaassen
Gary Feiss
Edwin Florencia
Errol P. Prens
Jacobus Burggraaf
Martijn B.A. vanDoorn
Robert Rissmann
Matthijs Moerland
author_sort Tessa Niemeyer‐van der Kolk
title Omiganan Enhances Imiquimod‐Induced Inflammatory Responses in Skin of Healthy Volunteers
title_short Omiganan Enhances Imiquimod‐Induced Inflammatory Responses in Skin of Healthy Volunteers
title_full Omiganan Enhances Imiquimod‐Induced Inflammatory Responses in Skin of Healthy Volunteers
title_fullStr Omiganan Enhances Imiquimod‐Induced Inflammatory Responses in Skin of Healthy Volunteers
title_full_unstemmed Omiganan Enhances Imiquimod‐Induced Inflammatory Responses in Skin of Healthy Volunteers
title_sort omiganan enhances imiquimod‐induced inflammatory responses in skin of healthy volunteers
publisher Wiley
series Clinical and Translational Science
issn 1752-8054
1752-8062
publishDate 2020-05-01
description Omiganan (OMN; a synthetic cationic peptide) and imiquimod (IMQ; a TLR7 agonist) have synergistic effects on interferon responses in vitro. The objective of this study was to translate this to a human model for proof‐of‐concept, and to explore the potential of OMN add‐on treatment for viral skin diseases. Sixteen healthy volunteers received topical IMQ, OMN, or a combination of both for up to 4 days on tape‐stripped skin. Skin inflammation was quantified by laser speckle contrast imaging and 2D photography, and molecular and cellular responses were analyzed in biopsies. IMQ treatment induced an inflammatory response of the skin. Co‐treatment with OMN enhanced this inflammatory response to IMQ, with increases in perfusion (+17.1%; 95% confidence interval (CI) 5.6%–30%; P < 0.01) and erythema (+1.5; 95% CI 0.25%–2.83; P = 0.02). Interferon regulatory factor‐driven and NFκB‐driven responses following TLR7 stimulation were enhanced by OMN (increases in IL‐6, IL‐10, MXA, and IFNɣ), and more immune cell infiltration was observed (in particular CD4+, CD8+, and CD14+ cells). These findings are in line with the earlier mechanistic in vitro data, and support evaluation of imiquimod/OMN combination therapy in human papillomavirus‐induced skin diseases.
url https://doi.org/10.1111/cts.12741
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