UV Radiation-induced Immunosuppression Research Articles

Development and characterization of novel 1-(1-Naphthyl)piperazine-loaded lipid vesicles for prevention of UV-induced skin inflammation

1-(1-Naphthyl)piperazine (1-NPZ) has shown promising effects by inhibiting UV radiation-induced immunosuppression. Ultradeformable vesicles are recent advantageous systems capable of improving the (trans)dermal drug delivery. The aim of this study was to investigate 1-NPZ-loaded transethosomes (NPZ-TE) and 1-NPZ-loaded vesicles containing dimethyl sulfoxide (NPZ-DM) as novel delivery nanosystems, and to uncover their chemopreventive effect against UV-induced acute inflammation. Their physicochemical properties were evaluated as follows: vesicles size and zeta potential by dynamic and electrophoretic light scattering, respectively; vesicle deformability by pressure driven transport; rheological behavior by measuring viscosity and I-NPZ entrapment yield by HPLC. In vitro topical delivery studies were performed in order to evaluate the permeation profile of both formulations, whereas in vivo studies sought to assess the photoprotective effect of the selected formulation on irradiated hairless mice by measuring myeloperoxidase activity and the secretion of proinflammatory cytokines.Either NPZ-TE or NPZ-DM exhibited positive results in terms of physicochemical properties. In vitro data revealed an improved permeation of 1-NPZ across pig ear skin, especially by NPZ-DM. In vivo studies demonstrated that NPZ-DM exposure was capable of preventing UVB-induced inflammation and blocking mediators of inflammation in mouse skin. The successful results here obtained encourage us to continue these studies for the management of inflammatory skin conditions that may lead to the development of skin cancers.

The Immune-Modulating Cytokine and Endogenous Alarmin Interleukin-33 Is Upregulated in Skin Exposed to Inflammatory UVB Radiation

The cellular and molecular mechanisms by which UV radiation modulates inflammation and immunity while simultaneously maintaining skin homeostasis is complex and not completely understood. Similar to the effects of UV, IL-33 has potent immune-modulating properties that are mediated by the downstream induction of cytokines and chemokines. We have discovered that exposure of mice in vivo or human skin samples ex vivo to inflammatory doses of UVB induced IL-33 expression within the epidermal and dermal skin layers. Using a combination of murine cell lines and primary human cells, we demonstrate that both UV and the oxidized lipid platelet activating factor induce IL-33 expression in keratinocytes and dermal fibroblasts. Highlighting the significance of these results, we found that administering IL-33 to mice in vivo suppressed the induction of Th1-mediated contact hypersensitivity responses. This may have consequences for skin cancer growth because UV-induced squamous cell carcinomas that evade immunological destruction were found to express significantly higher levels of IL-33. Finally, we demonstrate that dermal mast cells and skin-infiltrating neutrophils closely associate with UV-induced IL-33-expressing fibroblasts. Our results therefore identify and support a role for IL-33 as an important early danger signal produced in response to inflammation-inducing UV radiation.

UV Radiation-Induced Immunosuppression Is Greater in Men and Prevented by Topical Nicotinamide

UV radiation-induced immunosuppression augments cutaneous carcinogenesis. The incidence of skin cancer continues to increase despite increased use of sunscreens, which are less effective at preventing immunosuppression than sunburn. Using the Mantoux reaction as a model of skin immunity, we investigated the effects of solar-simulated (ss) UV and its component UVA and UVB wavebands and tested the ability of topical nicotinamide to protect from UV-induced immunosuppression. Healthy, Mantoux-positive volunteers were UV-irradiated on their backs, with 5% nicotinamide or vehicle applied to different sites in a randomized, double-blinded manner. Subsequent Mantoux testing at irradiated and adjacent unirradiated sites enabled measurement of UV-induced immunosuppression with and without nicotinamide. Suberythemal ssUV caused significant immunosuppression, although component UVB and UVA doses delivered independently did not. Men were immunosuppressed by ssUV doses three times lower than those required to immunosuppress women. This may be an important cause of the higher skin cancer incidence and mortality observed in men. Topical nicotinamide prevented immunosuppression, with gene chip microarrays suggesting that the mechanisms of protection may include alterations in complement, energy metabolism and apoptosis pathways. Nicotinamide is a safe and inexpensive compound that could be added to sunscreens or after-sun lotions to improve protection from immunosuppression. immunosuppression.JID JOURNAL CLUB ARTICLE: For questions, answers, and open discussion about this article, please go to http://network.nature.com/group/jidclub

Silymarin inhibits UV radiation-induced immunosuppression through augmentation of interleukin-12 in mice

We have shown previously that silymarin, a plant flavonoid, inhibits UVB-induced photocarcinogenesis in mice. As UVB-induced immunosuppression has been implicated in the development of skin cancer, we investigated whether silymarin can modulate the effects of UVB radiation on the immune system. Treatment of C3H/HeN mice with topically applied silymarin (0.5 or 1.0 mg/cm(2)) or silibinin, a major component of silymarin, markedly inhibited UVB (180 mJ/cm(2))-induced suppression of contact hypersensitivity response in a local model of immunosuppression and had a moderate inhibitory effect in a systemic model of contact hypersensitivity. Silymarin reduced the UVB-induced enhancement of the levels of the immunosuppressive cytokine, interleukin (IL)-10, in the skin and draining lymph nodes and enhanced the levels of the immunostimulatory cytokine, IL-12. Intraperitoneal injection of mice treated with silymarin with an endotoxin-free neutralizing anti-IL-12 antibody abrogated the protective effects of the silymarin against UVB-induced suppression of the contact hypersensitivity response. Furthermore, the treatment of silymarin did not prevent UVB-induced suppression of the contact hypersensitivity response in IL-12 knockout mice but prevented it in their wild-type mice. Moreover, i.p. injection of IL-12 to silymarin-treated or non-silymarin-treated IL-12 knockout mice resulted in an enhanced response to contact hypersensitivity compared with the response in mice that were exposed to either UVB alone or silymarin plus UVB. These data indicate for the first time that silymarin has the ability to protect mice from UVB-induced immunosuppression and that this protective effect is mediated, at least in part, through IL-12.

Notes from the Arbeitsgemeinschaft Dermatologische Forschung (ADF), Berlin,

Notes from the Arbeitsgemeinschaft Dermatologische Forschung (ADF), Berlin,

Prevention of UV Radiation-Induced Immunosuppression by IL-12 Is Dependent on DNA Repair

Prevention of UV Radiation-Induced Immunosuppression by IL-12 Is Dependent on DNA Repair

Measurement of In Vivo Sunscreen Immune Protection Factors in Humans

This study investigates the level of protection provided by sunscreens against solar-simulated UV radiation-induced immunosuppression in humans. The in vivo immune protection factors (IPF) of two broad-spectrum sunscreens were determined by assessing their ability to prevent UV-induced suppression of nickel contact hypersensitivity (CHS) in 15 nickel-allergic volunteers. Each volunteer was irradiated on unprotected skin of the back with different doses of UV daily for 4 days. Multiples of these UV doses were concurrently delivered to sunscreen-treated sites on the contralateral back. Nickel patches were then applied to both irradiated sites and adjacent, unirradiated control sites. Nickel-induced erythema at each site was measured 72 h later with a reflectance spectrometer. Comparison of the nickel reactions of irradiated and unirradiated skin revealed linear UV dose-responses for immunosuppression in both unprotected and sunscreen-treated skin. The minimum level of immunosuppression that can be reliably detected with this method is 20%. Therefore, the UV dose that reduces mean nickel CHS by 20% is the minimal immune suppression dose (MISD). Sunscreen IPF were determined by dividing the mean MISD of sunscreen-treated skin by that of unprotected skin. The sunscreens, with sun protection factors of 9 and 24, had IPF of 6.5 and > 25, respectively.

Measurement of In Vivo Sunscreen Immune Protection Factors in Humans

This study investigates the level of protection provided by sunscreens against solar-simulated UV radiation-induced immunosuppression in humans. The in vivo immune protection factors (IPF) of two broad-spectrum sunscreens were determined by assessing their ability to prevent UV-induced suppression of nickel contact hypersensitivity (CHS) in 15 nickel-allergic volunteers. Each volunteer was irradiated on unprotected skin of the back with different doses of UV daily for 4 days. Multiples of these UV doses were concurrently delivered to sunscreen-treated sites on the contralateral back. Nickel patches were then applied to both irradiated sites and adjacent, unirradiated control sites. Nickel-induced erythema at each site was measured 72 h later with a reflectance spectrometer. Comparison of the nickel reactions of irradiated and unirradiated skin revealed linear UV dose–responses for immunosuppression in both unprotected and sunscreen-treated skin. The minimum level of immunosuppression that can be reliably detected with this method is 20%. Therefore, the UV dose that reduces mean nickel CHS by 20% is the minimal immune suppression dose (MISD). Sunscreen IPF were determined by dividing the mean MISD of sunscreen-treated skin by that of unprotected skin. The sunscreens, with sun protection factors of 9 and 24, had IPF of 6.5 and >25, respectively.

The effects of two UVB radiation-absorbing sunscreens on UV radiation-induced carcinogenesis, suppression of the contact hypersensitivity response and histological changes in the hairless mouse

The research summarised in this report suggests that the two UVB-absorbers, o-PABA and 2-EHMC, have different modes of protection against UV radiation-induced immunosuppression, carcinogenesis and histological alterations, that appear to be independent of their SPF values, within experimental limits. The UVB-absorber o-PABA appears offer a valuable level of protection against photocarcinogenesis.

Sunscreens Protect from UV‐Promoted Squamous Cell Carcinoma in Mice Chronically Irradiated with Doses of UV Radiation Insufficient to Cause Edema

Previously we reported that the broad-spectrum sunscreen microfine titanium dioxide (MTD) could completely protect C3H/HeJ mice from UV radiation-induced immunosuppression to a contact sensitizer. In contrast, 2-ethylhexyl p-methoxycinnamate (2-EHMC), a UVB-absorbing sunscreen, only partially protected the skin immune system. In this study we investigated further this differential protection of the skin immune system by comparing the ability of 2-EHMC and MTD to protect these mice from the promotion phase of tumorigenesis. The mice were initiated using a single subcarcinogenic dose of 7,12-dimethylbenz(alpha)anthracene (DMBA) followed by promotion with chronic low-dose solar-simulated UV radiation for 32 weeks. We used doses of UV insufficient to cause edema in order to simulate daily human exposure to solar UV radiation. Mice were observed for the appearance of squamous cell carcinomas for 48 weeks. The DMBA-initiation alone and DMBA-initiated, sunscreen-treated groups did not develop tumors. Ultra-violet alone induced the appearance of tumors in 46% of mice at week 48 and therefore some tumors were initiated by UV. Initiation with DMBA prior to UV irradiation enhanced tumorigenesis such that 87% of mice at week 48 had tumors. Both 2-EHMC and MTD completely protected these mice from UV-induced promotion as well as from complete carcinogenesis despite the different UV-absorption spectra of the sunscreens and their differential abilities to protect from UV-induced immuno-suppression. Furthermore, we have shown that, if UV exposure is not increased to compensate for tolerance to edema, protection from tumorigenesis is afforded by sunscreens.

Evidence that sunscreens prevent UV radiation-induced immunosuppression in humans. Sunscreens have their day in the sun

Evidence that sunscreens prevent UV radiation-induced immunosuppression in humans. Sunscreens have their day in the sun

Evidence That Sunscreens Prevent UV Radiation-Induced Immunosuppression in Humans

IT has been known for over two decades that induction of malignant skin tumors in rodents by midrange UV radiation (UVB radiation, 280 to 320 nm) involves not only an oncogenic event within the epidermis but also specific immunologic changes that serve to prevent or inhibit a vigorous immune response against the incipient tumor by the host immune system. 1 Ultraviolet B—induced tumors in mice are highly immunogenic and fail to grow when transplanted to syngeneic recipients. 2-4 Indeed, the transplanted tumors are destroyed and immunologic memory against the transplanted tumor can be detected. This observation led to a series of studies aimed at understanding why these immunogenic tumors grow in the primary host. UV RADIATION INDUCES SPECIFIC IMMUNOLOGIC CHANGES IN MICE Experiments performed in the 1970s by Kripke 2,3 and Roberts et al 4 demonstrated that prolonged and repetitive exposure to UVB radiation results not only in the appearance