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UV-Aid as a preventative for seasonal illnesses

Abstract

Seasonal illnesses contribute to billions of dollars in lost productivity and thousands of life-years lost yearly across the world. Recent studies suggest a role for low levels of UVA exposure in enhancing the activity of the immune system within the nasal mucosae. Thus, this review is aimed at compiling the current evidence on the benefits of UVA mucosal exposure using UV-Aid® which emits approximately 25 mW/cm2 of 365nm UVA light for durations of 5-10 seconds resulting in exposures of 125-250 mJ/cm2.

Introduction

Worldwide, seasonal illnesses lead to lost productivity, hospitalizations, high health care spending, and thousands of deaths, with increasing infections as the seasons change(1-4). Epidemiological studies have linked the yearly fluctuation in flu & seasonal illness incidence to high-risk stratification, pandemic spread and ease of viral transmission(1, 2, 5, 6). Further, recent mathematical modeling studies suggest a significant link between climate, reduced sunlight exposure, and increased incidence of seasonal illnesses(2). Yearly, the incidence of seasonal illness, including ear infections, colds and influenza, results in more than 3.1 million hospitalized days, 31.4 million outpatient visits, $10.4 billion in annual direct medical costs, projected lost earnings greater than $16.3 billion, and an average of 610,660 life-years lost due to annual seasonal illness epidemics(4, 7, 8). There is an overwhelming total economic impact of more than $120 billion annually spent on all seasonal illnesses (including both direct and indirect expenditures) within the United States alone(7, 8). Furthermore, during the cold season productivity for workers and students has been reported to reduce by 26.4% with a jump to 44.5% absenteeism(9). Taken together, these reports bring up the critical inquiry of how to reduce incidence of seasonal illnesses rather than simply gritting our teeth and bearing the inevitable. 

This information led us to inquire whether there is a way to solve this epidemic using biomimicry. Nature emulates the perfect model of harnessing the most energetic rays of sunlight, UVB and most importantly to our interest, UVA. Intriguingly, recent studies have shown evidence that UVA radiation may critically contribute to host immunity via activation of the first line of host defense, the innate immune system, and via mobilization of the adaptive immune cells known as T cells(10, 11). Our interest is primarily found in how UVA sunlight radiation leads to immune system activation and responsiveness or prevention of seasonal illness. Here, we review how recent work indicates a supportive role of UVA radiation in preventing seasonal illnesses and the compelling evidence supporting the preemptive use of a biomimic technology that provides only UVA rays to activate the innate immune system, the first line of defense to seasonal illnesses.

It is critical to consider, as we begin to discuss prevention of seasonal illnesses, via targeting of the ear, nose, and throat (ENT), other methods of intercepting disease that have been staples of public health throughout the years. Handwashing and taking of supplements have been shown, among some reports, to reduce the risk of contracting upper respiratory tract infections(12). However, many of these reports are coincidental and recent research on the spread of rhinovirus infection (RV), RV associated common colds, staphylococcus aureus, and influenza are inconclusive at best(13-15). In fact, the recent work of research groups at Wake Forest and University of Virginia, elucidate a strong link between the spread of these detrimental seasonal illnesses and nasal dispersals which occur when the infected individual coughs or sneezes(13-15). These studies reveal that more care is needed to activate the host’s innate and adaptive immune system at the areas of highest vulnerability to airborne infectious particles, the mucous membranes of the ENT tracts.

UVA versus UVB, the good and the bad

Sunlight can be broken down into two predominant forms of UV radiation, UVA (320-400 nanometers (nm)) and UVB (280-320nm)(16-19). UV-induced alterations of human biology have been well studied. While both UVA and UVB radiation are able to potently modulate the immune system(10), the main focus of past research has been on the deleterious effects of UVB radiation. The impact of UVB radiation, which is primarily absorbed by the epidermis(20, 21), includes direct DNA damage via breakage or pyrimidine dimerization, induction of mutations leading to melanoma formation, and oxidative damage related to the excessive creation of free radicals(16, 21-25). Contradictory to the negative impact of UVB, UVA radiation has been shown to have numerous clinical benefits. UVA has been shown to reduce blood pressure via arterial vasodilation(21, 26, 27) and induce positive inflammatory responses via leukocyte migration(28-30), hydrogen peroxide (H2O2) induced phagocytosis(30, 31), monocyte release of chemokines and cytokines(30, 32, 33), activation of NFkB which assists in activation of immune and acute inflammatory response proteins that play a key role in countering seasonal illnesses(34, 35), and directing the function of wound healing neutrophils(30, 36). UVA exposure generates super-oxide (O2) which is converted into immune-modulating H2O2 via superoxide dismutase (SOD). Upon this conversion, H2O2 promotes proinflammatory immune responses to bacterial and viral instigators of seasonal illness(30, 37). Furthermore, UVA has been shown to inhibit histamine, a critical component to seasonal illness, release from leukocytes via moderation of SOD function, at exposures of 5,000 to 125,000mj/cm2 in two independent studies (38, 39). The reported negative associations of UVA exposure, such as inhibition of proinflammatory cytokines, UVA-induced double strand DNA breaks, and induction of ROS to detrimental levels are reported at levels much higher levels, approximately 1000x, that which is received with the beneficial exposure from UV-Aid® which will be discussed in more detail below(23, 38, 39).

Safety of UVA exposure

                The role of UV light in killing bacteria has long been associated with the destruction of its DNA via double stranded DNA (dsDNA) breaks. However, further research has shown that it is the specific wavelength range of the UVB light that results in DNA damage.  UVA light exposure, the light source used in UV-Aid®, when examined in multiple models from transgenic mouse models to zebrafish have been indicated as potentially beneficial to the host system and much less likely than UVB to result in melanoma formation(16, 24). Further, while UVB absorbs into the DNA resulting in direct breakage of the genetic backbone and mutation, UVA is less carcinogenic, penetrates further into the dermis and leads to an upregulation of reactive oxygen species (ROS)(40). The levels of exposure proffered by the UV-Aid® are sufficient to generate healthy ROS levels that are sufficient to activate the immune response in the nasal and mucosal passages without resulting in DNA damage and apoptotic cell death(16, 37, 41). Specifically, the UVA dosage shown to be benign by De Fabo et al (2004), is up to 120 times greater than a dose of the UV-Aid®. UV-Aid® emits approximately 25 mW/cm2 of 365nm UVA light for durations of 5-10 seconds resulting in exposures of 125-250 mJ/cm2. A corroborating study at MD Anderson reveals supportive data that the nasal mucosa is equally responsive and resistant to short-term effects of UV radiation as the epidermis of human skin(42). These results, found using short term exposure to UVA and following patients for up to one month, revealed that UV radiation, already in use for allergic rhinitis, may also be beneficial for preventing or treating seasonal illnesses(42).

UVA light enhances immune cell defense through H2O2 production

                It is well documented that UVB rays directly damage DNA leading to mutagenesis, however, UVA exposure penetrates much deeper than the epidermal layer and the full effect of this exposure remains unclear (17, 23, 43). While it is known that UVA radiation can lead to increased production of hydrogen peroxide (H2O2) and free radicals, often considered deleterious to cell survival (30), recent studies have shown alternative functions for UVA induced H2O2 ­production (30, 37, 44-46). These recent studies underline the effect that UVA induced H2O2 production has on dendritic cells, T cells, and monocytic immune cells (30, 37, 44-46). As the gradient of H2O2 rises in biological systems, to non-apoptotic levels, it activates molecular pathways, such as the Src kinase pathway  and Ca2+ mobilization in T cells (46), the NFkB signal in monocytes (35), and monocyte release of HMGB1 (32), which enhance the infection fighting activity of the immune system.

H2O2 and lymphocytes

                While it has long been accepted that sunlight allows humans to generate vitamin D, associated with health benefits, it has only recently come to light that UV exposure, specifically UVA radiation (320nm-400nm), has the potential to increase T cell motility (46). T cells are densely packed in normal skin and ENT mucosal layers with the highest ENT density found near the paranasal sinus cavities (46, 47). These clusters of T cells play the pivotal role of immune surveillance for foreign contaminants, such as those viruses and bacteria which lead to the development of seasonal illnesses (48). T cells located in the mucosae of the ENT system are considered to be the first line of defense to invading pathogens, however, there are numerous reports that the T cells normally located in the ENT mucosae exhibit increased expression of epithelial adhesion molecules, stabilizing the motility of T cells which may contribute to the heightened frequency of airway allergies and seasonal illness contraction (49). To enhance the responsiveness of T cells to cold and influenza insults it is necessary to modify immunity by enhancing the proliferation and mobility of responder T cells, studies testing this hypothesis have shown striking decreases in the symptoms of cold and flu with increased proliferation & mobilization of T cells using natural means (46, 50).

                UVA exposure leads to increased hydrogen peroxide production, a member of the reactive oxygen species (ROS) family, that drives oxidative metabolism. In in vitro studies, it has been shown that UVA radiation leads to photoactivation of H2O2 ­in T cells (46). This H2O2 leads to a downstream cascade that activates Src kinases via intracellular modification of cysteines or inhibition of CD45 (51, 52). Furthermore, UV exposure results in morphological changes in T cells which result in enhanced T cell motility. The Phan group shows that the experimental exposure of T cells to the laboratory light source resulted in extension of the lamellipodia, an essential organelle for T cell migration (46, 53). This increase in T cell motility is linked intricately with H2O2 dependent Lck pathway activation (46). Taken together, these data indicate that the short-term exposure of the ENT mucosae may benefit individuals via enhancing the activation and mobilization of T cells to generate a preventative environment.

H2O2 and monocytes

                In addition to the high tissue residency of T cells, there is a large presence of monocytic innate immune resident cells in the ENT mucosa. These monocytic cells are largely antigen presenting cells (APCs), including dendritic cells and macrophages, and neutrophils (54, 55). The professional APCs help to regulate the robust T cell response in the mucosa so that this cytotoxic response remains directed towards pathogens rather than leading to an attack of harmless environmental or self-antigens (54, 56). The recognition of pathogens by APCs results in T cell activation and increased pro-inflammatory cytokine production. H2O2 and oxidative stress generated by UVA has been shown to increase pro-inflammatory cytokine pathway, NFkB (30, 35).

                Oxidative stress and H2O2 production via UVA exposure activate genes involved in both the redox-sensitive transcription factor family, including NFkB, and the release of proinflammatory cytokines & matrix metalloproteinases, all of which contribute to the downstream activation and mobilization of adaptive immune T cells (29, 30). Additionally, phagocytic neutrophils are activated by the presence of environmental H2O2. Upon H2O2 exposure, these cells are primed to kill foreign pathogens via ROS generation following phagocytic activity (30). The understanding that UVA has the potential to activate the innate immune response to pathogens and trigger downstream activation of the adaptive T cell response is essential and promising in our attempt to provide evidence that seasonal illnesses may be preventable with the use of technology such as UV-Aid® to activate the first line of defense against pathogens.

Conclusions: Stay healthy naturally and safely with UV-Aid light

The potential for a novel, non-invasive, and inexpensive method for preventing the onslaught of seasonal illness opens a promising venue for research and poses many questions of how to best implement technology such as UV-Aid® as a standard prevention. The most obvious question this brings about is how well does UV-Aid® function to prevent seasonal illness in a clinical and epidemiological study.  We hypothesize that UV-Aid® will assist in reducing the prevalence of seasonal illness and result in minimizing the losses associated with high incidence. Research supports the notion that UV-Aid® may strongly contribute to the priming of the mucosal immune system to respond more rapidly to pathogen insults thus reducing the chance of host infection (30, 46).

The molecular mechanism by which low levels of UV radiation provided by UV-Aid® activates the innate and adaptive immune response reduces the risk of detrimental outcomes, such as DNA damage and apoptosis inducing levels of ROS. Regulation of T cell response is controlled by APCs, which are activated to recognize and present pathogens to their adaptive immune system counterparts via upregulation of H­2O2 dependent pathways such as NFkB. T cells are also directly influenced by UVA exposure via enhancement of motility. This motility is both directly and indirectly driven by UVA exposure. Direct enhancement of lamellipodia and activation of the Src and Lck pathways enhance motility as does the indirect increase in matrix metalloproteinase production by monocytic cells(29, 30, 46). These responses of the immune system could be responsible for an enhanced barrier blocking pathogens from invading the host system through the ENT mucosae.

The data reviewed here suggests a strong association for a novel approach to preventing seasonal illnesses. Therapeutically enhancing the mucosal immune system to rapidly respond to and eliminate pathogens, particularly involving a small, inexpensive, easily transportable piece of technology such as UV-Aid® is a game changer for the cold and flu season.

 

Kevin McGuire, President 

UV Technologies, LLC  

 


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