A deep dive into UV-based phototherapy: Mechanisms of action and emerging molecular targets in inflammation and cancer

Vieyra-Garcia, Pablo A.; Wolf, Peter

doi:10.1016/j.pharmthera.2020.107784

Cited by 64 publications

(60 citation statements)

References 695 publications

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“…Phototherapy has had considerable success in controlling inflammatory skin conditions by local proapoptotic, immunomodulatory, antipruritic, antifibrotic, propigmentary and pro-prebiotic effects [reviewed in ( 2 , 46 )]. Following exposure of individuals to sunlight or phototherapy, there are also changes in several cell types in blood, indicating that UVR has immunological effects beyond the skin.…”

Section: Discussionmentioning

confidence: 99%

More Than Effects in Skin: Ultraviolet Radiation-Induced Changes in Immune Cells in Human Blood

Hart

Norval

2021

Front. Immunol.

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Cells of the skin and circulation are in constant two-way communication. Following exposure of humans to sunlight or to phototherapy, there are alterations in the number, phenotype and function of circulating blood cells. In this review, only data obtained from human studies are considered, with changes induced by UV radiation (UVR) exposure described for phagocytic leukocytes and peripheral blood mononuclear cells plus their component T and B cells, natural killer cells and dendritic cells. These immune modulations illustrate the potential of UVR to have therapeutic effects beyond the skin, and that sunlight exposure is an important environmental influence on human health.

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Section: Discussionmentioning

confidence: 99%

More Than Effects in Skin: Ultraviolet Radiation-Induced Changes in Immune Cells in Human Blood

Hart

Norval

2021

Front. Immunol.

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“…[4] Externally applied ultraviolet light therapy is an approved treatment for several atopic, inflammatory and dysplastic dermatologic disorders. [5] In preclinical experiments, ultraviolet-A (UVA) exposure under monitored conditions (i.e. specific intensity, peak wavelength, exposure time and distance to target tissue), reduces bacteria, fungi, and viruses including coronavirus-229E but does not harm human ( in vitro) or murine ( in vivo) columnar epithelial cells.…”

Section: Introductionmentioning

confidence: 99%

Endotracheal application of ultraviolet A light in critically ill severe acute respiratory syndrome coronavirus-2 patients: A first-in-human study

Rezaie

Melmed

Leite³

et al. 2021

Preprint

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Background: Promising preclinical experiments show that, under specific and monitored conditions, ultraviolet-A (UVA) exposure reduces certain bacteria, fungi, and viruses including coronavirus-229E without harming mammalian columnar epithelial cells. We aimed to evaluate the safety and effects of UVA therapy administered by a novel device via endotracheal tube in critically ill subjects with SARS-CoV-2 infection. Methods: Five newly intubated mechanically ventilated adults with SARS-CoV-2 infection, with an endotracheal tube size 7.5mm or greater, were treated with UVA for 20 minutes daily for 5 days, and followed for 30 days. Results: Five subjects were enrolled (mean age 56.6yrs, 3 male). At baseline, all subjects scored 9/10 on the WHO clinical severity scale (10=death) with predicted mortality ranging from 21 to 95%. Average log changes in endotracheal viral load from baseline to day 5 and day 6 were -2.41 (range -1.16 to -4.54; Friedman P=0.002) and -3.20 (range -1.20 to -6.77; Friedman P<0.001), respectively. There were no treatment-emergent adverse events. One subject died 17 days after enrollment due to intracranial hemorrhagic complications of anticoagulation while receiving extracorporeal membrane oxygenation. The remaining subjects clinically improved and scored 2, 4, 5, and 7 on the WHO scale at day 30. In these subjects, the slope of viral load reduction during UVA treatment correlated with the slope of improvement in clinical WHO severity score over time (Spearman rho=1, P<0.001). Conclusion: In this first-in-human study, endotracheal UVA therapy under specific and monitored settings, was safe with a significant reduction in respiratory SARS-CoV-2 viral burden over the treatment period.

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“…External UVA light therapy is effective in patients with atopic dermatitis [23] and other skin disorders [24] , and is FDA-approved for the treatment of conditions such as psoriasis, eczema and skin lymphoma [25] . To explore the potential of internal UVA light therapy to treat microbial infections, we recently tested NB-UVA efficacy against a variety of bacterial, fungal and viral pathogens in vitro , including coronavirus-229E [12] .…”

Section: Discussionmentioning

confidence: 99%

Ultraviolet-A light reduces cellular cytokine release from human endotracheal cells infected with Coronavirus

Leite¹,

Pimentel²,

Mathur

et al. 2021

Photodiagnosis and Photodynamic Therapy

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Background An important clinical feature of coronavirus disease 2019 (COVID-19) is hypercytokinemia (cytokine storm). We previously showed that narrow band ultraviolet-A (NB-UVA) treatment salvages coronavirus (CoV)-229E-infected human tracheal cells, and that daily endotracheal NB-UVA therapy reduced severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) levels in human subjects, with improved clinical outcomes. Here, we examined NB-UVA effects on cytokine release during CoV-229E infection. Methods Primary human tracheal epithelial cells were transfected with CoV-229E, then exposed to 2 mW/cm 2 NB-UVA for 20 minutes every 24h, either 3 or 4 times. Secreted cytokine/chemokine levels were analyzed in supernatants harvested from CoV-229E-infected/UVA-exposed cells 24h after the last UVA treatment, and from matched non-infected/UVA-exposed controls, CoV-229E-infected/non-exposed controls, and non-infected/non-exposed (naïve) controls. Metabolic pathway/downstream prediction analyses were also performed. Results Pro-inflammatory cytokines interleukin(IL)-6 and tumor necrosis factor (TNF), and chemokines IL-8, monocyte chemoattractant protein-1 (MCP1), and interferon gamma-induced protein 10 (IP-10), were significantly increased in CoV-229E-infected cells, and significantly decreased following NB-UVA treatment. Interferon(IFN)-α2, IFN-γ, and IL-10 were not upregulated in response to CoV-229E. Metabolic pathway predictions indicated hypercytokinemia as the top inflammatory response in CoV-229E-infected cells, whereas the top predicted pathway in CoV-229E-infected/UVA-exposed cells was the recovery stage of severe acute respiratory syndrome. Conclusions Human tracheal epithelial cells infected with CoV-229E showed reduced cytokine secretions including IL-6, TNF, IL-8, and MCP-1, following NB-UVA exposure. This reduction of cytokine levels in vitro , coupled with previously identified reduced cell death in CoV-229E-infected/UVA-exposed cells, suggests that determining UVA effects on cytokine storm in human SARS-Co-V2 patients is warranted.

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A deep dive into UV-based phototherapy: Mechanisms of action and emerging molecular targets in inflammation and cancer

Cited by 64 publications

References 695 publications

More Than Effects in Skin: Ultraviolet Radiation-Induced Changes in Immune Cells in Human Blood

More Than Effects in Skin: Ultraviolet Radiation-Induced Changes in Immune Cells in Human Blood

Endotracheal application of ultraviolet A light in critically ill severe acute respiratory syndrome coronavirus-2 patients: A first-in-human study

Ultraviolet-A light reduces cellular cytokine release from human endotracheal cells infected with Coronavirus

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