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Vitamin D(3) and deconvoluting a rash
BACKGROUND: Adverse drug reactions are unpredictable immunologic events presenting frequent challenges to clinical management. Systemically administered cholecalciferol (vitamin D(3)) has immunomodulatory properties. In this randomized, double-blinded, placebo-controlled interventional trial of heal...
Autores principales: | , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
American Society for Clinical Investigation
2023
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9977299/ https://www.ncbi.nlm.nih.gov/pubmed/36692020 http://dx.doi.org/10.1172/jci.insight.163789 |
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author | Ernst, Madison K. Evans, Spencer T. Techner, Jose-Marc Rothbaum, Robert M. Christensen, Luisa F. Onay, Ummiye Venus Biyashev, Dauren Demczuk, Michael M. Nguyen, Cuong V. Honda, Kord S. McCormick, Thomas S. Tsoi, Lam C. Gudjonsson, Johann E. Cooper, Kevin D. Lu, Kurt Q. |
author_facet | Ernst, Madison K. Evans, Spencer T. Techner, Jose-Marc Rothbaum, Robert M. Christensen, Luisa F. Onay, Ummiye Venus Biyashev, Dauren Demczuk, Michael M. Nguyen, Cuong V. Honda, Kord S. McCormick, Thomas S. Tsoi, Lam C. Gudjonsson, Johann E. Cooper, Kevin D. Lu, Kurt Q. |
author_sort | Ernst, Madison K. |
collection | PubMed |
description | BACKGROUND: Adverse drug reactions are unpredictable immunologic events presenting frequent challenges to clinical management. Systemically administered cholecalciferol (vitamin D(3)) has immunomodulatory properties. In this randomized, double-blinded, placebo-controlled interventional trial of healthy human adults, we investigated the clinical and molecular immunomodulatory effects of a single high dose of oral vitamin D(3) on an experimentally induced chemical rash. METHODS: Skin inflammation was induced with topical nitrogen mustard (NM) in 28 participants. Participant-specific inflammatory responses to NM alone were characterized using clinical measures, serum studies, and skin tissue analysis over the next week. All participants underwent repeat NM exposure to the opposite arm and then received placebo or 200,000 IU cholecalciferol intervention. The complete rash reaction was followed by multi-omic analysis, clinical measures, and serum studies over 6 weeks. RESULTS: Cholecalciferol mitigated acute inflammation in all participants and achieved 6 weeks of durable responses. Integrative analysis of skin and blood identified an unexpected divergence in response severity to NM, corroborated by systemic neutrophilia and significant histopathologic and clinical differences. Multi-omic and pathway analyses revealed a 3-biomarker signature (CCL20, CCL2, CXCL8) unique to exaggerated responders that is suppressed by cholecalciferol and implicates IL-17 signaling involvement. CONCLUSION: High-dose systemic cholecalciferol may be an effective treatment for severe reactions to topical chemotherapy. Our findings have broad implications for cholecalciferol as an antiinflammatory intervention against the development of exaggerated immune responses. TRIAL REGISTRATION: clinicaltrials.gov (NCT02968446). FUNDING: NIH and National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS; grants U01AR064144, U01AR071168, P30 AR075049, U54 AR079795, and P30 AR039750 (CWRU)). |
format | Online Article Text |
id | pubmed-9977299 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2023 |
publisher | American Society for Clinical Investigation |
record_format | MEDLINE/PubMed |
spelling | pubmed-99772992023-03-02 Vitamin D(3) and deconvoluting a rash Ernst, Madison K. Evans, Spencer T. Techner, Jose-Marc Rothbaum, Robert M. Christensen, Luisa F. Onay, Ummiye Venus Biyashev, Dauren Demczuk, Michael M. Nguyen, Cuong V. Honda, Kord S. McCormick, Thomas S. Tsoi, Lam C. Gudjonsson, Johann E. Cooper, Kevin D. Lu, Kurt Q. JCI Insight Clinical Medicine BACKGROUND: Adverse drug reactions are unpredictable immunologic events presenting frequent challenges to clinical management. Systemically administered cholecalciferol (vitamin D(3)) has immunomodulatory properties. In this randomized, double-blinded, placebo-controlled interventional trial of healthy human adults, we investigated the clinical and molecular immunomodulatory effects of a single high dose of oral vitamin D(3) on an experimentally induced chemical rash. METHODS: Skin inflammation was induced with topical nitrogen mustard (NM) in 28 participants. Participant-specific inflammatory responses to NM alone were characterized using clinical measures, serum studies, and skin tissue analysis over the next week. All participants underwent repeat NM exposure to the opposite arm and then received placebo or 200,000 IU cholecalciferol intervention. The complete rash reaction was followed by multi-omic analysis, clinical measures, and serum studies over 6 weeks. RESULTS: Cholecalciferol mitigated acute inflammation in all participants and achieved 6 weeks of durable responses. Integrative analysis of skin and blood identified an unexpected divergence in response severity to NM, corroborated by systemic neutrophilia and significant histopathologic and clinical differences. Multi-omic and pathway analyses revealed a 3-biomarker signature (CCL20, CCL2, CXCL8) unique to exaggerated responders that is suppressed by cholecalciferol and implicates IL-17 signaling involvement. CONCLUSION: High-dose systemic cholecalciferol may be an effective treatment for severe reactions to topical chemotherapy. Our findings have broad implications for cholecalciferol as an antiinflammatory intervention against the development of exaggerated immune responses. TRIAL REGISTRATION: clinicaltrials.gov (NCT02968446). FUNDING: NIH and National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS; grants U01AR064144, U01AR071168, P30 AR075049, U54 AR079795, and P30 AR039750 (CWRU)). American Society for Clinical Investigation 2023-01-24 /pmc/articles/PMC9977299/ /pubmed/36692020 http://dx.doi.org/10.1172/jci.insight.163789 Text en © 2023 Ernst et al. https://creativecommons.org/licenses/by/4.0/This work is licensed under the Creative Commons Attribution 4.0 International License. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) . |
spellingShingle | Clinical Medicine Ernst, Madison K. Evans, Spencer T. Techner, Jose-Marc Rothbaum, Robert M. Christensen, Luisa F. Onay, Ummiye Venus Biyashev, Dauren Demczuk, Michael M. Nguyen, Cuong V. Honda, Kord S. McCormick, Thomas S. Tsoi, Lam C. Gudjonsson, Johann E. Cooper, Kevin D. Lu, Kurt Q. Vitamin D(3) and deconvoluting a rash |
title | Vitamin D(3) and deconvoluting a rash |
title_full | Vitamin D(3) and deconvoluting a rash |
title_fullStr | Vitamin D(3) and deconvoluting a rash |
title_full_unstemmed | Vitamin D(3) and deconvoluting a rash |
title_short | Vitamin D(3) and deconvoluting a rash |
title_sort | vitamin d(3) and deconvoluting a rash |
topic | Clinical Medicine |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9977299/ https://www.ncbi.nlm.nih.gov/pubmed/36692020 http://dx.doi.org/10.1172/jci.insight.163789 |
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