[HTML][HTML] Vitamin D3 and deconvoluting a rash
MK Ernst, ST Evans, JM Techner, RM Rothbaum… - JCI insight, 2023 - ncbi.nlm.nih.gov
JCI insight, 2023•ncbi.nlm.nih.gov
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 …
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 …
Abstract
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.
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