Mary Norval

The effects of ultraviolet radiation on the human immune system

The adverse outcome of increased ultraviolet (UV) irradiation on human health is currently of concern. While many experiments have been carried out in rodent models, fewer have been designed to test the effects of UV exposure in human subjects. This review concentrates on the modulations induced in the human immune system by UV, and outlines changes in antigen presentation by Langerhans cells and macrophages, in the activities of natural killer cells and T cells, and in cytokine regulation. Precautionary measures which might be taken to help protect people against the immunosuppressive action of UV irradiation are considered.

Environmental effects of ozone depletion and its interactions with climate change: progress report, 2011

The Environmental Effects Assessment Panel (EEAP) is one of three Panels that regularly informs the Parties (countries) to the Montreal Protocol on the effects of ozone depletion and the consequences of climate change interactions with respect to human health, animals, plants, biogeochemistry, air quality, and materials. The Panels provide a detailed assessment report every four years. The most recent 2014 Quadrennial Assessment by the EEAP was published as a special issue of seven papers in 2015 (Photochem. Photobiol. Sci., 2015, 14, 1-184). The next Quadrennial Assessment will be published in 2018/2019. In the interim, the EEAP generally produces an annual update or progress report of the relevant scientific findings. The present progress report for 2015 assesses some of the highlights and new insights with regard to the interactive nature of the effects of UV radiation, atmospheric processes, and climate change.

The role of urocanic acid in UV-induced immunosuppression: recent advances (1992-1994).

Abstract— Cis ‐ urocanic acid (UCA), formed in the epidermis by UV irradiation of trans‐UCA, has been implicated as a mediator of the immunosuppression induced by UV exposure of the skin. This review covers recent work in which the wavelength dependence of cis‐UCA formation, the interaction of UCA isomers with DNA, the effects of UCA isomers on the immune system and their interaction with histamine are examined. Results are frequently conflicting, particularly when considering the possible mode of action of cis‐UCA but, overall, a multifaceted role for UCA in immunomodulation by UV radiation is substantiated.

Biological effects of narrow-band (311 nm TL01) UVB irradiation: a review

The narrow-band UVB (TL01) lamp (311 nm emission) was developed for use in phototherapy, as an alternative to a broad-band UVB source and to photochemotherapy, both of which have significant side effects and carry a risk of carcinogenesis. This new lamp has proved to be particularly effective at clearing psoriasis. It is now acknowledged that the TL01 lamp is probably 2-3 times more carcinogenic per minimum erythema dose than broad-band UVB, but the cumulative dose required in therapy is considerably less than when using broad-band UVB sources. In terms of irradiation dose, the TL01 lamp is about 5-10-fold less potent than broad-band UVB for erythema induction, hyperplasia, oedema, sunburn cell formation and Langerhans cell depletion from skin. However, the broad-band UVB to TL01 potency ratio for cis-urocanic acid formation in the skin is approximately unity. In addition, the TL01 lamp, as used in phototherapy, has relatively more suppressive effects than broad-band UVB on systemic immune responses as judged by natural killer cell activity, lymphoproliferation and cytokine responses. However, the TL01 lamp is less effective at reducing epidermal antigen presentation, inducing dendritic cell migration to lymph nodes draining irradiated sites and suppressing contact hypersensitivity at the doses tested. Therefore the use of the TL01 lamp in phototherapy should be considered carefully after weighing up its diverse effects on the skin and immune system.

Cis-urocanic acid, a sunlight-induced immunosuppressive factor, activates immune suppression via the 5-HT2A receptor.

Exposure to UV radiation induces skin cancer and suppresses the immune response. To induce immune suppression, the electromagnetic energy of UV radiation must be absorbed by an epidermal photoreceptor and converted into a biologically recognizable signal. Two photoreceptors have been recognized: DNA and trans-urocanic acid (UCA). Trans-UCA is normally found in the outermost layer of skin and isomerizes to the cis isomer upon exposure to UV radiation. Although UCA was identified as a UV photoreceptor years ago, and many have documented its ability to induce immune suppression, its exact mode of action remains elusive. Particularly vexing has been the identity of the molecular pathway by which cis-UCA mediates immune suppression. Here we provide evidence that cis-UCA binds to the serotonin [5-hydroxytryptamine (5-HT)] receptor with relatively high affinity (Kd = 4.6 nM). Anti-cis-UCA antibody precipitates radiolabeled 5-HT, and the binding is inhibited by excess 5-HT and/or excess cis-UCA. Similarly, anti-5-HT antibody precipitates radiolabeled cis-UCA, and the binding is inhibited by excess 5-HT or excess cis-UCA. Calcium mobilization was activated when a mouse fibroblast line, stably transfected with the human 5-HT2A receptor, was treated with cis-UCA. Cis-UCA-induced calcium mobilization was blocked with a selective 5-HT2A receptor antagonist. UV- and cis-UCA-induced immune suppression was blocked by antiserotonin antibodies or by treating the mice with 5-HT2A receptor antagonists. Our findings identify cis-UCA as a serotonin receptor ligand and indicate that the immunosuppressive effects of cis-UCA and UV radiation are mediated by activation of the 5-HT2A receptor.

Does Chronic Sunscreen Use Reduce Vitamin D Production to Insufficient Levels

Exposure to ultraviolet B radiation in sunlight provides the mechanism for more than 90% of the vitamin D production in most individuals. Concern has been expressed in recent years that the widespread use of sunscreens, particularly those with high sun protection factors, may lead to a significant decrease in solar‐induced previtamin D3 in the skin, resulting in a vitamin D level which is considered insufficient for protection against a wide range of diseases. In this article the published evidence to support and to question this view is presented. It is concluded that, although sunscreens can significantly reduce the production of vitamin D under very strictly controlled conditions, their normal usage does not generally result in vitamin D insufficiency.

The consequences of UV-induced immunosuppression for human health.

Exposure to UV radiation can cause suppression of specific immune responses. The pathways leading to the down‐regulation are complex, starting from the absorption of UV photons by chromophores in the skin and ending with local and systemic changes in immune mediators, the generation of T and B regulatory cells and inhibition of effector and memory T cell activation. The consequences for human health are thought to be both beneficial and adverse. The former are illustrated by protection against polymorphic light eruption, and possible protection against T cell‐mediated autoimmune diseases and asthma. The latter are illustrated by skin cancer, cutaneous lupus erythematosus and infectious diseases including vaccination. Many outstanding questions remain in this rapidly developing and controversial area, not least what advice to give the general public regarding their sun exposure. While considerable advances have been made in the development of strategies that preserve the health benefits of sunlight exposure and decrease its detrimental effects, further research is required before optimal levels of protection are achieved.

Health effects from stratospheric ozone depletion and interactions with climate change

The potential health effects of elevated levels of ambient UV-B radiation are diverse, and it is difficult to quantify the risks, especially as they are likely to be considerably modified by human behaviour. Nevertheless epidemiological and experimental studies have confirmed that UV radiation is a definite risk factor for certain types of cataract, with peak efficacy in the UV-B waveband. The causal link between squamous cell carcinoma and cumulative solar UV exposure has been well established. New findings regarding the genetic basis of skin cancer, including studies on genetically modified mice, have confirmed the epidemiological evidence that UV radiation contributes to the formation of basal cell carcinomas and cutaneous melanomas, For the latter, animal models have demonstrated that UV exposure at a very young age is more detrimental than exposure in adulthood. Although suppression of certain immune responses has been recognised following UV exposure, the impact of this suppression on the control of infectious and autoimmune diseases is largely unknown. However, studies on several microbial infections have indicated significant consequences in terms of symptoms or reactivation of disease. The possibility that the immune response to vaccination could be depressed by UV-B exposure is of considerable concern. Newly emerging possibilities regarding interactions between ozone depletion and global climate change further complicate the risk assessments for human health but might result in an increased incidence of cataracts and skin cancer, plus alterations in the patterns of certain categories of infectious and other diseases.

UROCANIC ACID ANALOGUES AND THE SUPPRESSION OF THE DELAYED TYPE HYPERSENSITIVITY RESPONSE TO Herpes simplex VIRUS

Abstract

UROCANIC ACID AND IMMUNOSUPPRESSION

Urocanic acid, a molecule found at high concentration in the stratum corneum, acts as a photoreceptor for UV‐light, isomerizing from the naturally occurring trans‐lorm to the cis‐form. It has been proposed that cis‐urocanic acid may mediate the transient alteration in immune surveillance resulting in immunosuppression induced after UV‐irradiation, by interacting with immune cells locally and/or systemically to generate T cells with suppressor function. The evidence to support this hypothesis is summarized, and possible interactions of urocanic acid with immune cells and their outcome are discussed.