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1.
JCI Insight ; 8(2)2023 Jan 24.
Artículo en Inglés | MEDLINE | ID: mdl-36692020

RESUMEN

BACKGROUNDAdverse drug reactions are unpredictable immunologic events presenting frequent challenges to clinical management. Systemically administered cholecalciferol (vitamin D3) 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 D3 on an experimentally induced chemical rash.METHODSSkin 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.RESULTSCholecalciferol 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.CONCLUSIONHigh-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 REGISTRATIONclinicaltrials.gov (NCT02968446).FUNDINGNIH and National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS; grants U01AR064144, U01AR071168, P30 AR075049, U54 AR079795, and P30 AR039750 (CWRU)).


Asunto(s)
Colecalciferol , Exantema , Adulto , Humanos , Colecalciferol/farmacología , Método Doble Ciego , Resultado del Tratamiento , Exantema/inducido químicamente , Exantema/tratamiento farmacológico , Inflamación/tratamiento farmacológico
2.
Adv Exp Med Biol ; 996: 3-11, 2017.
Artículo en Inglés | MEDLINE | ID: mdl-29124686

RESUMEN

The use of ultraviolet (UV) light, for the treatment of skin conditions, dates back to the early 1900s. It is well known that sunlight can be of therapeutic value, but it can also lead to deleterious effects such as burning and carcinogenesis. Extensive research has expanded our understanding of UV radiation and its effects in human systems and has led to the development of man-made UV sources that are more precise, safer, and more effective for the treatment of wide variety of dermatologic conditions.


Asunto(s)
Rayos Láser/historia , Fotoquimioterapia/historia , Enfermedades de la Piel/historia , Rayos Ultravioleta/historia , Terapia Ultravioleta/historia , Animales , Diseño de Equipo , Historia del Siglo XIX , Historia del Siglo XX , Historia del Siglo XXI , Humanos , Rayos Láser/efectos adversos , Seguridad del Paciente , Fotoquimioterapia/efectos adversos , Fotoquimioterapia/instrumentación , Dosis de Radiación , Exposición a la Radiación/historia , Factores de Riesgo , Enfermedades de la Piel/tratamiento farmacológico , Enfermedades de la Piel/radioterapia , Resultado del Tratamiento , Rayos Ultravioleta/efectos adversos , Terapia Ultravioleta/efectos adversos , Terapia Ultravioleta/instrumentación
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