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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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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