No full-text available
To read the full-text of this research,
you can request a copy directly from the authors.
Estimation of the effect of increasing UVB exposure on the human immune system and related resistance to infectious diseases and tumours
Abstract
Exposure to UV light has, besides some beneficial effects (vitamin D production), many harmful effects on human health. UVB irradiation has been shown to suppress both systemic and local immune responses to a variety of antigens, including some microorganisms. However, it is still not known whether such immunomodulating effects may lead to an increase in the number and severity of certain tumours and/or infections in humans. We report herein the data provided by a project that was funded by the European Union (Programme Environment), and that was aimed at the estimation of the risk associated with increased UVB exposure due to ozone depletion regarding the deleterious effects on the immune system and related resistance to tumours and infections in humans. The data, obtained by the different research groups involved, were assembled and used to calculate for the first time a risk assessment for increased environmental exposure to UVB in human subjects.
... Exposure to UV radiation may cause various health hazards and suppress local and systemic immune responses. Several studies have shown that the artificial and also solar UV radiation can affect the activity and number of the lymphocyte subsets in human blood ( Garssen et al, 1998; Bogoljubov et al, 1994; Mutzhas et al., 1994). Since people like sunbathing in summer, assessment of accompanying health risks is important. ...
... The lymphocyte subsets, in which significant changes have been observed, are presented inTable 1. Also, a weak negative correlation (correlation coefficient 46%) between the individual total UV doses and the increase in the percentage of CD3 + HLA-DR + cells was observed: larger UV doses caused a smaller increase in the cell population. Garssen et al. (1998) reported a decrease in NK cells and an increase in HLA-DR + cells in blood as a consequence of sun radiation. The observed changes in CD3 + HLA-DR + and NK cells in our study were similar. Since statistically significant changes in CD3 + HLA-DR + cells due to UV radiation occurred, we would assign those changes in peripheral blood (at l ...
... Since CD4 + CD25 + cells may be related to the suppression of immune responses after UV exposure, the increase of those cells in our study may be associated with recurrent exposure to UV radiation. Seasonal fluctuations of lymphocyte subpopulations have been observed in healthy (Garssen et al., 1998) and HIV-infected persons (Termorshuizen et al., 2002). As our study was carried out only during summer months, it cannot be excluded that these were seasonal changes in which UV radiation may have an important role. ...
... Exposure to UV-B radiation, especially UV-B radiation, has many harmful effects on health.These may result in poorer performance, or even death, despite not being directly induced by exposure to UV-B radiation. UV-B radiation suppresses systemic and local immune responses to a variety of antigens, including microorganisms (Garssen et al., 1998;Hurks et al., 1994). In addition to suppressing T-cell-mediated immune reactions, UV-B radiation also affects nonspecific cellular immune defenses. ...
... Among the remaining 93 unique citations, 91 were excluded for the following reasons: 1. Eight did not report on cancer outcomes [31]-[38]; 2. Twenty four did not report on breast cancer outcomes [39]–[62]; 3.Twenty eight were not RCTs [63]–[90]; 4. Eighteen did not fulfill the inclusion criterion related to the intervention [22], [91]–[107]; 5. Thirteen were excluded because combining at least 2 among the previously described features (1 to 5) [18], [20], [108]–[118] (Figure 1). Only two trials fulfilled the inclusion criteria [21], [30]. ...
In recent years, the scientific evidence linking vitamin D status or supplementation to breast cancer has grown notably. To investigate the role of vitamin D supplementation on breast cancer incidence, we conducted a systematic review and meta-analysis of randomized controlled trials comparing vitamin D with placebo or no treatment. We used OVID to search MEDLINE (R), EMBASE and CENTRAL until April 2012. We screened the reference lists of included studies and used the "Related Article" feature in PubMed to identify additional articles. No language restrictions were applied. Two reviewers independently extracted data on methodological quality, participants, intervention, comparison and outcomes. Risk Ratios and 95% Confident Intervals for breast cancer were pooled using a random-effects model. Heterogeneity was assessed using the I(2) test. In sensitivity analysis, we assessed the impact of vitamin D dosage and mode of administration on treatment effects. Only two randomized controlled trials fulfilled the pre-set inclusion criteria. The pooled analysis included 5372 postmenopausal women. Overall, Risk Ratios and 95% Confident Intervals were 1.11 and 0.74-1.68. We found no evidence of heterogeneity. Neither vitamin D dosage nor mode of administration significantly affected breast cancer risk. However, treatment efficacy was somewhat greater when vitamin D was administered at the highest dosage and in combination with calcium (Risk Ratio 0.58, 95% Confident Interval 0.23-1.47 and Risk Ratio 0.93, 95% Confident Interval 0.54-1.60, respectively). In conclusions, vitamin D use seems not to be associated with a reduced risk of breast cancer development in postmenopausal women. However, the available evidence is still limited and inadequate to draw firm conclusions. Study protocol code: FARM8L2B5L.
... In humans and experimental animals, UVR can cause local and whole-body immunosuppression (UNEP, 1998). Cellular immunity has been shown to be affected by ambient doses of UVR (Garssen et al., 1998). Concern exists that UVR-induced immunosuppression could influence patterns of infectious disease. ...
... UV-B suppresses both systemic and local immune responses to a variety of antigens, including microorganisms (Hurks et al. 1994, Garssen et al. 1998). In addition to suppressing T-cell-mediated immune reactions, UV-B also affects nonspecific cellular immune defences. ...
The objectives of the research program reported upon here were (1) to measure ambient levels of UV radiation and determine which variables most strongly affected its attenuation in the waters of the estuary and Gulf of St. Lawrence, Canada; and (2) to investigate the potential direct impacts of UV radiation on species of crustacean zooplankton and fish whose early life stages are planktonic. In this geographic region, productivity-determining biophysical interactions occur in the upper 0 to 30 m of the water column. Measurements of the diffuse attenuation coefficients forultraviolet-B radiation (UV-B, 280 to 320 nm) at various locations in this region indicated maximum 10% depths (the depth to which 10% of the surface energy penetrates at a given wavelength) of 3 to 4 m at a wavelength of 310 nm. Organisms residing in this layer-including the eggs and larvae of Calanus finmarchicus and Atlantic cod Gadus morhua- are exposed to biologically damaging levels of UV radiation. As a result of these physical and biological characteristics, this system offered a relevant opportunity to assess the impacts of UV on subarctic marine ecosystem. Eggs of C. finmarchicus were incubated under the sun, with and without the W-B and/or UV-A (320 to 400 nm) wavebands. UV-exposed eggs exhibited low percent hatching compared to those protected from UV: UV radiation had a strong negative impact on C. finmarchicus eggs. Further, percent hatching in UV-B-exposed eggs was not significantly lower than that in eggs exposed to UV-A only: under natural sunlight, UV-A radiation appeared to be more detrimental to C. finmarchicus embryos than was UV-B. In analogous experiments with Atlantic cod eggs, exposure to UV-B produced a significant negative effect. However, W-A had no negative effect on cod eggs. Additional experiments using a solar simulator (SS) revealed high wavelength-dependent mortality in both C, finmarchicus and cod embryos exposed to UV. The strongest effects occurred under exposures to wavelengths below 312 nm. At the shorter wavelengths (<305 nm) W-B-induced mortality was strongly dose-dependent, but (for both C, finmarchicus and cod) not significantly influenced by dose-rate. Thus, at least within the Limits of the exposures under which the biological weighting functions (BWFs) were generated, reciprocity held. The BWFs derived for UV-B-induced mortality in C. finmarchicus and cod eggs were similar in shape to the action spectrum for UV-B effects on naked DNA. Further, the wavelength-dependence of DNA damage was similar to that for the mortality effect. These observations suggest that W-induced mortality in C, finmarchicus and cod eggs is a direct result of DNA damage. There was no evidence of a detrimental effect of UV-A radiation in these SS-derived results. A mathematical model that includes the BWFs, vertical mixing of eggs, meteorological and hydrographic conditions, and ozone depletion, indicates that UV-induced mortality in the C, finmarchicus egg population could be as high as 32.5%, while the impact on the cod egg population was no more than 1.2%. Variability in cloud cover, water transparency (and the variables that affect it), and vertical distribution and displacement of planktonic organisms within the mixed layer can all have a greater effect on the flux of W-B radiation to which they are exposed than will ozone layer depletion at these latitudes. Our observations indicate that C. finmarchicus and cod eggs present in the first meter of the water column (likely only a small percentage of the total egg populations) are susceptible to UV radiation. However, although exposure to UV can negatively impact crustacean zooplankton and ichthyoplankton populations, these direct effects are Likely minimal within the context of all the other environmental factors that produce the very high levels of mortality typically observed in their planktonic early Life stages. The impact of indirect effects - which may well be of much greater import - has yet to be evaluated.
... These may result in poorer performance, or death, even though they are not directly induced by the UV exposure. UV-B suppresses both systemic and local immune responses to a variety of antigens, including microorganisms (Hurks et al. 1994, Garssen et al. 1998). In addition to suppressing T-cell-mediated immune reactions, UV-B also affects nonspecific cellular immune defences. ...
The objectives of the research program reported upon here were (1) to measure ambient levels of UV radiation and determine which variables most strongly affected its attenuation in the waters of the estuary and Gulf of St. Lawrence, Canada; and (2) to investigate the potential direct impacts of UV radiation on species of crustacean zooplankton and fish whose early life stages are planktonic. In this geographic region, productivity-determining biophysical interactions occur in the upper 0 to 30 m of the water column. Measurements of the diffuse attenuation coefficients for ultraviolet-B radiation (UV-B, 280 to 320 nm) at various locations in this region indicated maximum 10% depths (the depth to which 10% of the surface energy penetrates at a given wavelength) of 3 to 4 m at a wavelength of 310 nm. Organisms residing in this layer - including the eggs and larvae of Calanus finmarchicus and Atlantic cod Gadus morhua - are exposed to biologically damaging levels of UV radiation. As a result of these physical and biological characteristics, this system offered a relevant opportunity to assess the impacts of UV on subarctic marine ecosystems. Eggs of C. finmarchicus were incubated under the sun, with and without the UV-B and/or UV-A (320 to 400 nm) wavebands. UV-exposed eggs exhibited low percent hatching compared to those protected from UV: UV radiation had a strong negative impact on C. finmarchicus eggs. Further, percent hatching in UV-B-exposed eggs was not significantly lower than that in eggs exposed to UV-A only: under natural sunlight, UV-A radiation appeared to be more detrimental to C. finmarchicus embryos than was UV-B. In analogous experiments with Atlantic cod eggs, exposure to UV-B produced a significant negative effect. However, UV-A had no negative effect on cod eggs. Additional experiments using a solar simulator (SS) revealed high wavelength-dependent mortality in both C. finmarchicus and cod embryos exposed to UV. The strongest effects occurred under exposures to wavelengths below 312 nm. At the shorter wavelengths (< 305 nm) UV-B-induced mortality was strongly dose-dependent, but (for both C. finmarchicus and cod) not significantly influenced by dose-rate. Thus, at least within the limits of the exposures under which the biological weighting functions (BWFs) were generated, reciprocity held. The BWFs derived for UV-B-induced mortality in C. finmarchicus and cod eggs were similar in shape to the action spectrum for UV-B effects on naked DNA. Further, the wavelength-dependence of DNA damage was similar to that for the mortality effect. These observations suggest that UV-induced mortality in C. finmarchicus and cod eggs is a direct result of DNA damage. There was no evidence of a detrimental effect of UV-A radiation in these SS-derived results. A mathematical model that includes the BWFs, vertical mixing of eggs, meteorological and hydrographic conditions, and ozone depletion, indicates that UV-induced mortality in the C. finmarchicus egg population could be as high as 32.5%, while the impact on the cod egg population was no more than 1.2%. Variability in cloud cover, water transparency (and the variables that affect it), and vertical distribution and displacement of planktonic organisms within the mixed layer can all have a greater effect on the flux of UV-B radiation to which they are exposed than will ozone layer depletion at these latitudes. Our observations indicate that C. finmarchicus and cod eggs present in the first meter of the water column (likely only a small percentage of the total egg populations) are susceptible to UV radiation. However, although exposure to UV can negatively impact crustacean zooplankton and ichthyoplankton populations, these direct effects are likely minimal within the context of all the other environmental factors that produce the very high levels of mortality typically observed in their planktonic early life stages. The impact of indirect effects - which may well be of much greater import - has yet to be evaluated.
... Because UA and DNA coexist in that part of the animal most exposed to sunlight, it is vital to understand the photochemical interaction of these two skin chromophores. This becomes even more important in view of the fact that environmental factors are causing depletion of ozone layer that allows penetration of more UVB radiation from the sun to the earth (89)(90)(91). ...
... Specifically, intense, intermittent sun exposure (peeling sunburn) in childhood and adulthood appear to significantly contribute to the development of melanoma (Gilchrest et al., 1999; Armstrong and Kricker, 2001; Autier et al., 1997), while cumulative sun exposure (long-term outdoor working and suntanning ) appears responsible for the development of SCC (Rosso et al., 1996; Kricker et al., 1994; Gallagher et al., 1995b; Lavkar et al., 1995), while mixed effects of cumulative and intermittent sun exposure seem to account for the development of BCC (Rosso et al., 1996; Gallagher et al., 1995a; van Dam et al., 1999; Lavkar et al., 1995). Cumulative and intermittent sun damage is thought to significantly decrease the ability of the skin's immune system to repair chromosomal damage and detect and destroy potential cancerous cells (Grossman and Leffell, 1997; Garssen et al., 1998; Vermeer and Hurks, 1994). The Cancer Council of Queensland currently endorses six strategies to reduce cumulative and intermittent sun damage including: minimising time spent in the sun between 10am and 3pm; seeking shade; wearing suitable clothing that provides good sun protection; choosing a broad brim, legionnaire-style or bucketstyle hat that protects the face, neck and ears; wearing sunglasses; and applying SPF 30+ broad spectrum, water-resistant sunscreen 20 minutes before going out into the sun (Cancer Council Queensland, 2009). ...
Objective: To identify whether personal experience of skin cancer in people who regularly participate in recreational boating is associated with their level of midday sun exposure, current sun protective behaviours and sun-induced skin damage. Methods: Cross-sectional survey with 24-hour follow-up of recreational boat users who regularly go boating between 9am and 3pm. The study was conducted in Townsville, North Queensland (latitude 19S), during the summer of 2003. Of the 134 boat users approached, 124 consented to participate, with 5 later excluded from analysis (n=119, response rate=92%). Results: In comparison to people reporting no personal experience of skin cancer, people with personal experience of skin cancer were more likely to: (1) report spending fewer hours on the boat between 9am to 3pm (p=0.010), (2) report using a canopy during the boat trip (p=0.038), (3) report wearing sunglasses (p=0.013), and (4) spend more than one hour in the sun on a typical workday (p=0.059). People who reported having previous skin cancer were no more likely to use personal sun protection or have a lighter tan, and no less likely to experience sunburn from the boat trip, than people not having skin cancer. Conclusions: During recreational boating, people who reported previous skin cancer were more likely to use a shade structure and spend less time in the sun during peak UVR hours (particularly those who typically worked indoors), but not to use more individual sun protection practices excepting sunglasses, than people not having skin cancer.
... . Also impaired resistance to bacterial, fungal and parasitic pathogens has been implicated in exposure to UVB radiation (5)(6)(7)(8). It is well documented that fish exposed to solar or simulated UVB radiation suffer from sunburns, dermal lesions and fungal infection of the skin (9)(10)(11). ...
The effects of short-term exposure to ultraviolet B (UVB) radiation on lymphocyte-related parameters were studied under controlled laboratory conditions using roach (Rutilus rutilus), a cyprinid teleost, as the model fish. In vitro lymphoproliferative responses stimulated with a T-cell–specific mitogen, concanavalin A (ConA), or a B-cell–specific activator, lipopolysaccharide (LPS), were decreased in exposed fish. Also nonstimulated proliferation was lower than in unexposed fish. ConA-activated responses returned to normal levels within 7 days after exposure, but LPS-activated responses were reduced throughout the 14 day follow-up. The capability of UVB-exposed fish to produce an antibody response was studied by intraperitoneal immunization with bovine γ-globulin (BGG). The concentration of anti-BGG antibodies in plasma as well as the number of anti-BGG–specific antibody-secreting cells in the spleen or blood were not decreased in fish exposed either to a single dose of UVB prior to immunization, or to single dose of UVB prior to immunization followed by three additional doses after immunization. Immunoglobulin M (IgM) production, when assayed as plasma IgM level or as the number of IgM-secreting cells in the spleen or blood, was not suppressed after exposure to UVB irradiation. These results indicate that a single dose of UVB or short-term exposure to UVB irradiation has no negative effects on IgM production or reactivity against antigen administered via the intraperitoneal route. However, the suppression of in vitro lymphoproliferative responses suggest that exposure to UVB has the potential to interfere with lymphocyte-related functions in fish.
... These may result in poorer performance, or death, even though they are not directly induced by the UV exposure. UV-B suppresses both systemic and local immune responses to a variety of antigens, including micro-organisms (Hurks et al. 1994; Garssen et al. 1998 ). In addition to suppressing T-cell-mediated immune reactions, UV-B also affects nonspecific cellular immune defences. ...
Over the past 10–15 years, solar ultraviolet B (UV-B, 290–320 nm) levels have increased significantly at mid-latitude areas
of the Northern and Southern Hemispheres. These increases in UV-B are linked to reductions of stratospheric ozone. Although
the variables that affect UV-B penetration into water columns are still under active investigation, there are typically strong
correlations between dissolved organic carbon (DOC), chlorophylla (chla), and UV attenuation. This is particularly significant in the context of possible UV-B impacts on marine coastal systems,
since DOC and chla are usually much more highly concentrated in these waters than in the open ocean. Observations indicate that the early life
stages of crustacean zooplankton and ichthyoplankton present in the first meter of coastal water columns (like only a small
percentage of the total population) are susceptible to UV-B radiation. Variability in cloud cover, water transparency (and
the variables that affect it), and vertical distribution and displacement of organisms within the mixed layer have a greater
effect on the flux of UV-B radiation to which plankton are exposed than will ozone layer depletion. Although exposure to UV-B
can negatively affect planktonic organisms, such directs effects are likely minimal in coastal zones, and within the context
of all the other environmental factors that produce the very high levels of mortality typically observed in their early life
stages. Indirect effects (e.g., UV-B-induced reduction in the nutritional quality of the food base) have not as yet been adequately
evaluated.
... These may result in poorer performance, or death, even though they are not directly induced by the UV exposure. UV-B suppresses both systemic and local immune responses to a variety of antigens, including micro-organisms (Hurks et al. 1994; Garssen et al. 1998). In addition to suppressing T-cell-mediated immune reactions, UV-B also affects non-specific cellular immune defences. ...
A rapidly growing number of studies indicate that solar ultraviolet B radiation (280–320 nm, UV-B), at current levels, is
harmful to aquatic organisms and may reduce the productivity of marine ecosystems (e.g. Siebeck et al. 1994; Häder 1997; DeMora et al. 2000). Such UV-B-induced decreases in productivity have been reported for bacterioplankton, phytoplankton, heterotrophs and zooplankton,
the key intermediary levels of marine food chains (Damkaer 1982; Thomson 1986; Cullen and Neale 1994; Chalker-Scott 1995; Smith and Cullen 1995; Häder 1997). Analogous studies on the planktonic (often neustonic) early life history stages of crustacean zooplankton and ichthyoplankton,
although much rarer, indicate that exposure to levels of UV-B currently incident at the earth’s surface could result in higher
mortality that may lead to poorer recruitment to the adult populations of marine and freshwater fishes (Pommeranz 1974; Hunter et al. 1981; Hunter et al. 1982; Williamson et al. 1997; Walters and Ward 1998; Zagarese and Williamson 2000). This chapter focuses on the effects of UV (280–400 nm) radiation on crustacean zooplankton and ichthyoplankton in subarctic
marine ecosystems.
... Experimental animal data show that ultraviolet radiation (UVR) at doses relevant to outdoor exposure may affect specific cellular immune responses and reduce the resistance to viral, bacterial and parasitic agents [1,2]. It has also been shown that exposure to artificial UVR or sunlight may suppress important immune parameters in humans [3,4,5]. ...
We investigated whether exposure to solar UVR would influence the occurrence of skin infections in a cohort of renal transplant recipients. In various experimental studies, exposure to UVR was demonstrated to possibly cause immunosuppression and impaired resistance to infections. We expected that such effects could be demonstrated more easily in the patients who were already immunocompromised. The lifetime cumulative exposure to solar UVR was estimated on the basis of self-reported data: the season in which the diagnosis was made was regarded as providing a rough estimate of the exposure just prior to or at the time of infection. In a Multivariate Poisson Regression Model for repeated measurements, we found the highest incidence of Herpes Simplex, Herpes Zoster and fungal/yeast infections to be associated with the summer season. There was no consistent association found between the lifetime cumulative estimate of exposure and the infection. The seasonal fluctuation may be due to the circannual rhythm in ambient levels of UVR. Dit rapport beschrijft een studie waarin werd nagegaan of blootstelling aan zonlicht van invloed is op het optreden van huidinfecties in een cohort niertransplantatie patienten. Dit deden wij, daar uit diverse met name experimentele studies bekend is dat blootstelling aan ultraviolette straling (UV) een immuunsuppressie en een verlaagde weerstand tegen diverse infecties kan veroorzaken. Wij verwachtten dat in deze groep patienten door de reeds aanwezige immuunsuppressie dergelijke effecten eerder aan het licht zullen treden. De 'life-time' cumulatieve blootstelling aan zonlicht werd retrospectief geschat op basis van zelf-gerapporteerde gegevens; seizoen van diagnose werd gezien als ruwe maat voor de blootstelling vlak voor of op het moment van het optreden van de infectie. In een multivariaat Poisson regressie model voor herhaalde waarnemingen werd gevonden dat Herpes Simplex-, Herpes Zoster- en schimmel/gist infecties het meest in het zonnige seizoen gevonden werden, terwijl er geen duidelijke samenhang bleek te zijn met de 'life-time' cumulatieve maat voor zonlicht blootstelling. De gevonden seizoenseffecten zouden samen kunnen hangen met het jaarritme in de UV belasting.
... The ozone layer prevents any UVC radiation (Ͻ280 nm), and a large proportion of the UVB radiation, from reaching the Earth's surface. The thinning of the protective ozone layer has been accompanied by increasing levels of penetrating UVB radiation in some parts of the world, and has led to concern over the resultant effects on human health (Garssen et al, 1998). Exposure to UVB has been shown to suppress cell-mediated immunity, frequently using contact hypersensitivity (CH) (Noonan and De Fabo, 1992) and delayed-type hypersensitivity (DTH) (Howie et al, 1986) assays, and to induce tolerance to antigens encountered after the irradiation (Baadsgaard et al, 1990). ...
Solar radiation contains ultraviolet B (280-315 nm) and ultraviolet A (ultraviolet AII, 315-340 nm; ultraviolet AI, 340-400 nm) wavebands. Ultraviolet B is known to suppress certain aspects of cell mediated immunity. Using three ultraviolet lamps (the broad-band ultraviolet B TL-12, the narrow-band ultraviolet B TL-01 and an ultraviolet AI source), we investigated the dose and waveband dependencies for the suppression of contact hypersensitivity to oxazolone and delayed-type hypersensitivity to herpes simplex virus, plus the formation of cis-urocanic acid in C3H/HeN mice. A single exposure of 1500 J/m2 TL-12 or 10,000 J/m2 TL-01 or 500,000 J/m2 ultraviolet AI corresponded to 1 minimum erythema dose in this mouse strain. The percentage of cis-urocanic acid of the total urocanic acid rose from a background level of 1.7% to 40% with 1000 J/m2 TL-12 or 10,000 J/m2 TL-01, but only 17% cis-urocanic acid was obtained with 500,000 J/m2 ultraviolet AI. The contact hypersensitivity response was significantly suppressed after a minimum dose of 5000 J/m2 TL-12 or 50,000 J/m2 TL-01 or 500,000 J/m2 ultraviolet AI. The delayed-type hypersensitivity response was suppressed by a minimum dose of 100 J/m2 TL-12 or 10,000 J/m2 TL-01 or 1000 J/m2 ultraviolet AI. So, whereas a low dose of ultraviolet AI reduced the delayed-type hypersensitivity response, a 500-fold higher dose was required to suppress contact hypersensitivity. There was no correlation between the suppression of these responses and the concentration of cis-urocanic acid in the skin. Thus different mediators may modulate the various immune responses affected by ultraviolet exposure, depending on the wavelength of the radiation.
... Exposure to ultraviolet light (280 – 400 nm), especially UVB, has many harmful effects on animal and human health. In addition to induction of skin cancers due to mutagenic effects, combined with a decrease in immune surveillance against the tumour cells, UVB suppresses both systemic and local immune responses to a variety of antigens, including micro-organisms (Hurks et al., 1994; Garssen et al., 1998). UVB exposure impairs the immunological resistance to infectious disease in rats and humans, aggravates pulmonary tuberculosis, triggers herpes simplex virus infection, and increases viral warts in patients with papilloma infections (Jeevan and Kripke, 1993 ). ...
Ultraviolet B radiation penetrates into water and can affect fish health and the immune system, as is the case with mammals. Teleost fish, the roach, were exposed to UVB irradiation in aquariums and a panel of immune parameters was determined. In addition to altered blood picture and respiratory burst by blood leukocytes, changes were noted also in major lymphatic organs. Respiratory burst and natural cytotoxicity activity of head kidney granulocytes and mitogen-activated proliferation of splenic lymphocytes were suppressed. Although mostly transitory, some parameters remained suppressed for the following 2 weeks. Ultraviolet A radiation had only minor effects. The stress induced by UVB may be involved in the modulation of immune parameters.
... In addition, UV exposure has been demonstrated to impair resistance to bacterial, viral, parasitic, and fungal infections. Importantly, the effects of UV radiation are not restricted to skin-associated infections, but are also found in systemic (nonskin-associated) infections (Garssen et al, 1998). Owing to the fact that UVB is not able to penetrate much beyond the epidermis, UVB-induced immunosuppression is likely to be mediated by cells or their products or photo-activated factors present in the skin. ...
Exposure to ultraviolet radiation can modulate immune responses in animal and humans. Remarkably, the ultraviolet-induced immunosuppression is not restricted to the exposed skin but is also found at other body sites, i.e., systemic immunosuppression. Effects of ultraviolet radiation on infections cannot be determined by experimentation on humans, but the effects of ultraviolet on vaccination may serve as a model. Moreover, it is important in its own right to assess whether ultraviolet radiation affects vaccination responses. In this study the effect of ultraviolet B exposure on the development of immune responses after hepatitis B vaccination in human volunteers was investigated. To this end, 191 human volunteers were vaccinated against hepatitis B with the Engerix-B vaccine. Ninety-seven of them were prior to the first vaccination exposed to ultraviolet B on 5 consecutive days with one personal minimal erythema dose per day. At several time-points before and after the ultraviolet B exposure regimen and the vaccination, blood samples were taken. Parameters for specific as well as nonspecific cellular and humoral immunity were analyzed. It was demonstrated that ultraviolet B exposure prior to hepatitis B vaccination did not alter the cellular (lymphocyte stimulation test) nor the humoral (antibody titers) immune response against hepatitis B surface antigen significantly. In contrast, contact hypersensitivity to diphenylcyclopropenone was significantly suppressed after ultraviolet B exposure, as was natural killer cell activity. These latter results confirm earlier findings and demonstrate immunosuppressive effectiveness of the ultraviolet regimen. In summary, although natural killer cell activity and contact hypersensitivity responses were suppressed, the ultraviolet B radiation protocol did not alter the humoral nor the cellular immune responses against hepatitis B surface antigen after vaccination.
In the present article various consequences of acid rain had
been discussed. Acid rain effects on buildings and monuments,
water and aquatic animals, human health, plants and soils
were reviewed. Most effects found in between pH a range 3 to 5.
Step must be taken to control acid rain.
Environment protection and preservation of ecological
balance have always a matter of awareness which can be
depicted from Vedas. In modern time, when the development is
on its full phase and parallel the natural resources are being
exhausted, then we have to realise the environmental protection
as first priority for sustainable life on earth. When
environmental pollution is discusses, those created by different
industries in various forms must be focussed. Although many
measures have been taken so far which is having a positive
impact but we must also think to enrich the environment and
biodiversity by using some innovative methods in the direction
of green chemistry. Paint industry which is a raw material
intensive, uses a large number of ingredients and many of them
harm the environment in direct or indirect way. In last few
decades huge reduction in VOC emission has been observed.
Various measure has been taken to combat and reduce the
environmental pollution like water-based paints, radiation
curable coatings, powder coatings etc. In this paper the
pollution created by paint manufacturing and application
industry is discussed and also the adoption of new technologies
to overcome its effect
The information on how much total solar energy and its ultraviolet component can be acquired from the Sun at particular locations is vital for climatology, ecology, health-care but also for some branches of modern industry (e.g. constructions, solar power technologies, materials science, pharmacy, optometry and optics). The Discrete Fourier Transform applied to study UV index (UVI) time series in the last solar cycle at selected locations (71 in Europe and 114 in the World) has revealed periodicity and correlation between the amplitude and latitude. The main frequency peak with amplitude varying from 0.963 to 5.625 shows the UVI periodicity of 315–316 days at each location. The greatest variation in UVI occurs at two latitude bands distanced by 65° (Northern hemisphere from 30° to 50° and Southern hemisphere from −50° to −20°); the lowest variation is observed near the equatorial region.
A completely novel method for a comparative analysis of UVI measured by satellites (Nimbus-7/TOMS (Total Ozone Mapping Spectrometer), 1978–1991; Meteor-3/TOMS, 1991–1995; Earth-Probe/TOMS, 1996–2005) for the whole globe in the range from 1978 to 2005, has been developed and applied. A few mathematical metrics (Manhattan, Euclidean, Bhattacharyya, Hellinger) applied for the studies of monthly averaged maps of UVI from 1978 to 2005 reveal different character of UVI variations at selected latitudes and on the global scale. The topological Pompeiu–Hausdorff metric was introduced as a measure and used to visualize the variations on UVI maps. This metric, tolerant to small positions errors, also cancels the errors which come from those in positioning satellites, blank regions caused by the satellite motion or clouds.
The feed forward, multilayered supervised artificial neural network dedicated to the reconstruction of world maps of erythemal Ultraviolet index (UV index) was constructed and trained using three different sets of data selected from 1978 to 2005. A combined analysis made using Manhattan, Euclidean, Bhattacharyya, Hellinger and topological Pompeiu–Hausdorff metrics has revealed large unconnected and inhomogeneous areas of high variability in UVI maps. The modeling of the long term variation in UVI during the whole sun activity cycle helped to understand trends and predict the direction of future variations in UV radiation level. The quality of prediction was evaluated using a newly proposed approach based on Pompeiu–Hausdorff metric.
The depletion in stratospheric ozone and changes in life-styles are likely to lead to an increased exposure to sunlight, including the UV-B waveband. Such irradiation may induce immunomodulation and therefore have adverse effects on human health. Alterations in immune responses could affect not only photocarcinogenesis but also resistance to infections, certain allergies and autoimmunity, and vaccination efficacy. In the present study, the risk of increased UV-B exposure has been estimated with respect to the resistance to a bacterial (Listeria monocytogenes) and a viral (herpes simplex virus) infection. The data indicate that suberythemal UV-B irradiation can have significant effects on immune responses to certain infectious diseases in human subjects.
Photochemistry reviews photo-induced processes that have relevance to the above wide-ranging academic and commercial desciplines, and interests in chemistry, physics, biology and technology. In order to provide easy access to this vast and varied literature, Photochemistry comprises sections sub-divided by chromophore and reaction type, and also a comprehensive section on polymer photochemistry. Throughout emphasis is placed on useful applications of photochemistry. Specialist Periodical Reports provide systematic and detailed review coverage in major areas of chemical research and are compiled by teams of leading experts - a unique service for the active research chemist.
UV radiation is an important problem in climatology, ecology but also has direct effect on human health. A novel method for analysis and prediction of global erythemal UV for clear-sky at noon at any localisation, expressed as the UV index, has been proposed. The supervised artificial neural networks (ANN) were trained using purely experimental astronomical parameters (input: solar elevation, total ozone level, aerosol index, reflectivity and required output: erythemal local noon UV irradiance expressed as the UV index) for all dates from a 3-year representative period (2001–2003) collected by Total Ozone Mapping Spectrometer (TOMS). The input data from the 3-year period provide three sets of 1095 grids, each consisting of 288×180 i.e. 56,764,800 training vectors for total ozone level, aerosol index, reflectivity, while the output data provide only one set of data of the same resolution. The trained network delivers a good long-term representation of the physical problem as it is able to predict clear-sky global UV index maps (UVI for any location and date) with an excellent accuracy close to the detection error (3%, 0.5 unit of UVI). The omission of data on aerosol index (slightly) and reflectivity (highly) deteriorates the quality of UVI prediction (MSPE error 6.4%, 1 unit of UVI) but also confirms the importance of total ozone level for the UVI prediction. The neglect of data on aerosol index and reflectivity evidently removes the inhomogeneities and results in smoother and less reliable UVI maps. Reflectivity plays a very important role in variation of UV radiation level. The results are presented in the form of 2D rectangular maps (WGS-84 projection) of UV index. The neural network approach to UVI forecasting and analysis yields reasonable results and can be considered as an alternative to traditional approaches mainly based on radiative-transfer or regression models.
The immunosuppressive effects of UVB irradiation have been well documented. The production of cytokines by keratinocytes is considered to play a major role in the induction of local as well as systemic immunosuppression. It is thought that partly due to the interaction of locally produced cytokines with antigen-presenting cells (APC) systemic effects, like antigen-specific tolerance, can be induced. In this study we examined the effect of UVB irradiation on cytokine profiles of peripheral APC as well as the functional consequences. Our results indicate that UVB irradiation impairs Th1-mediated immune responses in vivo by suppression of the systemic IL-12p70 production. Splenic APC from UVB-exposed mice showed an enhanced production of prostaglandin E2, IL-1, IL-6 and tumor necrosis factor-α after in vitro stimulation. Also, spleen cells from UVB irradiated IL-4 –/– mice showed increased IL-6 levels. These APC were less efficient in inducing IFN-γ production by CD4 T cells and suppressed IgM production by B cells. We conclude that the altered cytokine profile of peripheral APC can be responsible for the systemic effects of UVB irradiation on the Th1/Th2 balance as well as on B cell responses.
The UV-protection effect of green-tea dyed fabrics was reported in our previous studies. The chitosan was used as a natural mordant of cellulose fiber for green tea extract because chitosan is a natural bio-polymer. The increase in the UV protection property of summer cellulose fabrics, cotton and linen, upon the repetition of chitosan mordanting and green tea dyeing was observed. However, the physical property change would be followed by this repeated wet processing of the cellulose fabric. Therefore, the physical changes of the chitosan mordanted and green tea dyed cotton and linen fabrics were evaluated by KES-FB system. Tensile, shear, bending, compression, and surface characteristics were tested upon the repetition of mordanting and dyeing treatments. Linearity of tensile force increased in the treated cotton and linen samples. Tensile energy and resilience decreased in all treated fabrics. Shear stiffness increased in the treated cotton and linen in general. Shear hysteresis was increased in all cotton samples and some linen samples. In cotton, the bending rigidity in all treated cottons increased except C3G3. As the chitosan mordanting numbers increased, the bending rigidity tended to decrease. In linen, the bending rigidity and hysteresis increased in all treated samples. Compressional energy and resilience increased as the number of chitosan mordanting increased both in cotton and linen. This could be the result of the increase in thickness upon chitosan mordanting. Surface coefficient of friction increased in the treated cotton and linen in general. Surface roughness tended to increase in cotton.
As UV radiation to the earth increased over recent years, many adverse effects of UV radiation have been reported. There are needs to develop UV-protective apparel and accessaries to protect skin from these harmful effects. Cellulose is one of the most frequently worn fiber during summer time. However, celllulose shows very low UV-protective property especially in case of thin and low fabric content. In this study, UV-protective cellulose textiles were developed using chiotsan mordanting and green tea dyeing. The repetition effect of chitosan and green tea treatment were focused. Three different cellulose fibers, cotton, linen, and ramie, were used for this study. All chitosan mordanted and green tea dyed fabrics showed increases in UV-protective property. The color of fabrics tended to darker as the numbers of mordanting process and green tea dyeing increased. UV-protective property did not increase significantly upon the repetition of mordanting and green tea dyeing treatment except ramie fabric. UV protective property was persisted upon washfastness test in all three cellulose fiber types.
Los efectos de las radiaciones ultravioletas (UV) sobre el sistema inmunitario se conocen desde hace más de 40 años. No sólo agravan algunas enfermedades infecciosas, también ejercen un efecto promotor sobre el desarrollo de cánceres cutáneos. Sin embargo, los efectos inmunorreguladores de los UV son beneficiosos para la salud, ya que favorecen la tolerancia a los antígenos de contacto y modulan las reacciones autoinflamatorias o autoinmunitarias. Estos efectos inmunorreguladores se aprovechan, además, en el ámbito terapéutico. Los UV ejercen sus efectos inmunosupresores en diversos niveles de la respuesta inmunitaria innata y adaptativa. En primer lugar, las células de Langerhans (CL) epidérmicas que presentan el antígeno sufren alteraciones morfológicas y funcionales. Bajo el efecto de los UV, dichas células se dirigen a los ganglios periféricos, donde inducen la proliferación de linfocitos T supresores (citolíticos naturales [células NK, natural killer] y reguladores), produciendo citocinas inmunorreguladoras (interleucina 4 [IL-4] o IL-10, respectivamente). Los queratinocitos también son diana de los UV y secretan diversos mediadores solubles con actividades inmunosupresoras, entre los que se destaca la IL-10. A nivel molecular, el ácido desoxirribonucleico (ADN) es el cromóforo principal de los UV en la piel, y la formación de dímeros de pirimidina participa de forma directa en la inmunosupresión inducida por los UV. Éstos inducen también una fotoisomerización del ácido transurocánico en ácido cisurocánico, el cual puede adquirir propiedades inmunosupresoras. Los UV también interactúan con dianas citoplasmáticas y de membrana, capaces de modificar la transducción de señales o la transcripción de genes implicados en la respuesta inmunitaria. Aunque los mecanismos que intervienen en la inmunosupresión inducida por los UV se conocen cada vez mejor, todavía persisten numerosas incógnitas, sobre todo a raíz de la variedad de modelos experimentales y de las longitudes de onda aplicadas. Así, las radiaciones UVA también participan en estos fenómenos inmunosupresores, como ha sido demostrado en los experimentos de restauración de la respuesta inmunitaria tras la aplicación de filtros solares.
Los efectos de la radiación ultravioleta (UV) sobre el sistema inmunitario se conocen desde hace más de 30 años y son responsables no sólo del agravamiento de algunas enfermedades infecciosas sino también de la aparición de algunos tipos de cáncer de piel. La radiación UV ejerce sus efectos inmunosupresores en diferentes etapas de la respuesta inmunitaria. En primer lugar, las células de Langerhans de la epidermis que presentan el antígeno sufren alteraciones morfológicas, cuantitativas y funcionales puesto que, bajo el efecto de la radiación UV, migran hacia los ganglios periféricos donde ya no tienen la capacidad de inducir una estimulación de los clones linfocíticos Thl. Los queratinocitos también son el blanco de la radiación UV y secretan diversos mediadores solubles que tienen actividades inmunosupresoras, especialmente la interleucina (IL) 10 y el factor de necrosis tumoral α (TNFα). Además, la radiación UV causa una activación del complemento queratinocítico y la producción de neuropéptidos (monóxido de nitrógeno y el «péptido relacionado con el gen de la calcitonina” [CGTP]) que poseen una actividad inmunosupresora. En la piel humana, la IL-10 es producida fundamentalmente por los macrófagos CDI Ib que, tras una exposición a la radiación UV, infiltran la epidermis. Estos macrófagos son responsables de la inducción de una tolerancia. En la periferia, la radiación UV genera una población linfocítica Th2 que produce IL-10. Estos linfocitos ejercerían su actividad inmunosupresora induciendo la apoptosis de las células de Langerhans epidérmicas mediada por el sistema Fas/Fas ligando. Al nivel molecular, la radiación UV induce una fotoisomerización del ácido transurocánico en ácido cisurocánico, capaz de ejercer propiedades inmunosupresoras. Sin embargo, el ácido desoxirribonucleico celular sigue siendo el principal cromóforo de la radiación UV en la piel; en la inmunosupresión inducida por la radiación UV interviene la formación de dímeros de pirimidina. Asimismo, la radiación UV interactúa con los blancos citoplasmáticos y de las membranas, capaces de modificar la transducción de señales o la transcripción de los genes implicados en la respuesta inmunitaria. Aunque cada vez se conocen mejor los mecanismos que intervienen en la inmunosupresión inducida por la radiación UV, sigue habiendo numerosas incógnitas relacionadas fundamentalmente con la variedad de los modelos experimentales y con el tipo de longitudes de onda empleadas. De esta manera, se comprueba la participación de la radiación UV en estos fenómenos inmunosupresores como se demostró mediante las experiencias de restauración de la respuesta inmunitaria al aplicar filtros solares.
A compact and mobile optical spectrometer for the detection of total atmospheric ozone is described. The ozone column is determined by differential absorption of solar radiation at two adjacent UV wavelengths (328 and 329 nm). Measurements made during an 18 month period in South Germany confirm previous satellite data during the periods of October 1996 to February 1997, April 1997 to February 1998 and May 1998, but exhibit some ozone decrease in March 1997, as well as in April 1998, (C) 2000 Society of Photo-Optical Instrumentation Engineers. [S0091-3286(00)02807-5].
The depletion in stratospheric ozone and changes in life-styles are likely to lead to an increased exposure to sunlight, including the UV-B waveband. Such irradiation may induce immunomodulation and therefore have adverse effects on human health. Alterations in immune responses could affect not only photocarcinogenesis but also resistance to infections, certain allergies and autoimmunity, and vaccination efficacy. In the present study, the risk of increased UV-B exposure has been estimated with respect to the resistance to a bacterial (Listeria monocytogenes) and a viral (herpes simplex virus) infection. The data indicate that suberythemal UV-B irradiation can have significant effects on immune responses to certain infectious diseases in human subjects.
There is increasing interest in the many beneficial aspects of green tea to human such as anti-carcinogenic, anti-aggregant,
anti-allergic, anti-bacterial, anti-mutagenic, and anti-oxidant activities. Besides these beneficial aspects, it has been
reported that green tea ingredients, especially polyphenolic families (i.e., catechin), have some UV protection property both
in vivo and in topical applications. In this study, green tea extract was used as a dyeing stock for cotton and the UV protection
property of the dyed cotton fabric was examined. To increase the affinity of cotton fiber to the polyphenolic components in
the green tea extract, a natural biopolymer, chitosan, was used as mordanting agent. The effects of chitosan concentration
in mordanting on the dyeing characteristics and the UV protection property were examined. Chitosan mordanted green tea dyed
cotton showed better dyeing characteristic and higher UV protection property compared with the unmordanted green tea dyed
cotton. As the chitosan concentration in mordanting increased, the dyeing efficiency and the UV protection property also increased.
Therefore, adapting chitosan mordanting in green tea dyeing can increase the UV protection property of cotton fabrics to some
extent.
Basal cell carcinoma (BCC) is the most common skin malignancy encountered worldwide. We hypothesized that CXC chemokines, small cytokines involved in inducing directed leukocyte chemotaxis, could play a key role in the modulation of BCC growth. In this study, quantitative RT-PCR revealed that the chemokines CXCL9, 10, 11, and their receptor CXCR3 were significantly upregulated by an average 22.6-fold, 9.2-fold, 26.6-fold, and 4.9-fold, respectively in BCC tissue samples as compared with nonlesional skin epithelium. Immunohistochemistry analysis revealed that CXCR3, CXCL10, and CXCL11, but not CXCL9, colocalized with cytokeratin 17 (K17) in BCC keratinocytes. In addition, CXCR3 and its ligands were expressed in cells of the surrounding BCC stroma. The chemokines and K17 were also expressed in cultured human immortalized HaCaT keratinocytes. Exposure of HaCaT cells or primary BCC-derived cells to CXCL11 peptides in vitro significantly increased cell proliferation. In primary BCC-derived cell cultures, addition of CXCL11 progressively selected for K17+/CXCR3+ co-expressing cells over time. The expression of CXCR3 and its ligands in human BCC keratinocytes, the enhancement of keratinocyte cell proliferation by CXCL11, and the homogeneity of K17+ BCC cells in human BCC-isolated cell population supported by CXCR3/CXCL11 signaling all suggest that CXCR3 and its ligands may be important autocrine and/or paracrine signaling mediators in the tumorigenesis of BCC.
Ultraviolet B irradiation has serious consequences for cellular immunity and can suppress the rejection of skin tumors and the resistance to infectious diseases. DNA damage plays a crucial role in these immunomodulatory effects of ultraviolet B, as impaired repair of ultraviolet-B-induced DNA damage has been shown to cause suppression of cellular immunity. Ultraviolet-B-induced DNA damage is repaired by the nucleotide excision repair mechanism very efficiently. Nucleotide excision repair comprises two subpathways: transcription-coupled and global genome repair. In this study the immunologic consequences of specific nucleotide excision repair defects in three mouse models, XPA, XPC, and CSB mutant mice, were investigated. XPA mice carry a total nucleotide excision repair defect, whereas XPC and CSB mice only lack global genome and transcription-coupled nucleotide excision repair, respectively. Our data demonstrate that cellular immune parameters in XPA, XPC, and CSB mice are normal compared with their wild-type (control) littermates. This may indicate that the reported altered cellular responses in xeroderma pigmentosum patients are not constitutive but could be due to external factors, such as ultraviolet B. Upon exposure to ultraviolet B, only XPA mice are very sensitive to ultraviolet-B-induced inhibition of Th1-mediated contact hypersensitivity responses and interferon- production in skin draining lymph nodes. Lipopolysaccharide-stimulated tumor necrosis factor and interleukin-10 production are significantly augmented in both XPA and CSB mice after ultraviolet B exposure. Lymph node cell numbers were increased very significantly in XPA, mildly increased in CSB, and not in XPC mice. In general XPC mice do not exhibit any indication of enhanced ultraviolet B susceptibility with regard to the immune parameters analyzed. These data suggest that both global genome repair and transcription-coupled repair are needed to prevent immunomodulation by ultraviolet B, whereas transcription-coupled repair is the major DNA repair subpathway of nucleotide excision repair that prevents the acute ultraviolet-B-induced effects such as erythema.
When M10 cells derived from mouse lymph nodes were irradiated with the UVB lamp at a peak emission of 312 nm, the cell growth was suppressed in proportion to irradiation time (10-30 s) and cell apoptosis was also induced by the irradiation. Dynamic changes in 597 genes after exposing these cells to UVB irradiation were investigated by DNA array analysis using array membranes and a (33)P-labeling probe. After 2 h of irradiation, the gene expression in the cells was examined and compared with that in untreated cells. Radioactivity was analyzed using Array Gauge software. The data were further processed using software, EX-ARRAY, which was developed for extracting significant data from the results of 2 background-subtraction methods, i.e., global and local background subtraction. The number of genes suppressed under UV irradiation increased with irradiation time, while that of activated genes decreased. Finally, we confirmed 4 genes (HMG-14, CDX-2, MCP-3, and GRP-78) to be up-regulated and confirmed their activation by northern blot. We propose these genes as the new biomarkers of lymphocyte sensitive to UVB irradiation.
UV-B radiation suppresses cell-mediated immunity. Histidine forms trans-urocanic acid (trans-UCA) enzymatically in the stratum corneum. Photoisomerization of trans-UCA to cis-urocanic acid (cis-UCA) has been proposed for the initiation of an immunosuppressive process. Many microorganisms described in the literature metabolize histidine and/or trans-UCA. Our enrichment cultures of soil and sewage contain organisms that can degrade cis-UCA. We have tested microorganisms for degradation of cis-UCA, trans-UCA, or L-histidine when they are incorporated at 0.2% in nutrient broth. Six out of 10 selected genera isolated by our clinical microbiology laboratory degrade one or more of the imidazole substrates. We have cultured over 60 aerobic isolates from human skin. Of these, 33 degrade one or more of the three imidazole substrates and 12 degrade cis-UCA. Isolates from BALB/c mice are also active on cis-UCA. We have identified a cis-UCA-degrading bacterium as Micrococcus luteus. Four ATCC strains of M. luteus have been tested and three are active on histidine or trans-UCA; two are active on cis-UCA. Micrococci that degrade cis-UCA contain a new enzyme, cis-UCA isomerase, which converts the substrate to the trans-isomer. This enzyme provides access to the classical L-histidine degradation pathway. We hypothesize that an epidermal microflora that degrades L-histidine, trans-UCA, or cis-UCA influences the concentration of urocanic acids on the skin and, thus, affects immune suppression.
Exposure to UV is a recognised risk factor for skin cancer and it also induces immunosuppression to a variety of antigens encountered following the irradiation. The latter property has been demonstrated in rodent models of infections with the microbial agents including viruses, bacteria, protozoa and helminths. In the majority of cases the severity of the symptoms and the microbial load in the host are increased as a result of the immunomodulation. UV can also affect the pathogenesis of some natural microbial infections of human subjects, such as causing recrudescence of herpes simplex virus and contributing to the oncogenic potential of papillomaviruses. Sufficient data have been generated from the animal models to construct a risk assessment in humans for suppression of microbial immune responses induced by sunlight exposure. This estimation requires verification from epidemiological studies and from further work to assay modulation in human immunity to particular pathogens experienced before and after the UV radiation.
We have tested the hypothesis that exposure to ultraviolet light would inhibit T helper-1 (Th1) responses and stimulate T helper-2 (Th2) responses, and that thus in a mouse model of allergic (i.e. extrinsic) asthma (using ovalbumin [OVA] as the allergen) increased symptoms would be observed, while in a model of Th1-dependent occupational asthma (in which picryl chloride is the allergen) decreased symptoms would be observed. Whereas reduced interferon (IFN)-gamma production, decreased inflammatory responses in the airways, and reduced airway reactivity to nonspecific stimuli were observed in UV-preexposed picryl chloride sensitized and challenged mice, the results in the OVA model were less clear. Increased interleukin (IL)-10 production as a result of UV exposure was observed, together with unchanged IL-4 and IFN-gamma. In addition, decreased OVA-specific immunoglobin, IgG1 and IgE, titers were noted, as well as decreased nonspecific airway hyperreactivity. Eosinophilic inflammatory responses were not influenced. The results indicate that UV exposure can have systemic effects that influence ongoing immune responses in the respiratory tract. The effects are not only restricted to immune responses that are predominantly Th1 dependent (i.e. pulmonary delayed-type hypersensitivity and IFN-gamma production in response to picryl chloride) but also to immune response that are predominantly Th2 dependent, i.e. decreased specific IgE titers.
Herpes simplex virus (HSV) normally causes vescular lesions on mucocutaneous surfaces but can also cause encephalitis. The virus can reactivate from the latent state in neurons to form recrudescent lesions. One common stimulus for reactivation is exposure to sunlight. In the present study, the effects of irradiating rats with suberythemal ultraviolet (UV) before or after infecting them epidermally with HSV was investigated. Preexposure to UV impaired HSV-specific cellular immune responses, as indicated by delayed type hypersensitivity (DTH) and in vitro lymphoproliferation assays. However, the number and severity of the skin lesions were not altered. In contrast, exposure after infection did not affect cellular immunity but resulted in a large increase in the severity and number of lesions. In a second series of experiments, the effects of preirradiating with UV on HSV infection was examined using a route of inoculation which was not skin-associated, namely intranasal, allowing direct non-invasive access to the nervous system. It was found that suppressed DTH resulted, together with an increase in the incidence and severity of neurological symptoms and an increased viral load in the brain. Therefore, unlike the situation in the skin, irradiation of rats before intranasal inoculation led to a suppressed immune response to HSV which correlated with increased viral load and symptoms. These results indicate that the effects of UV may be dependent on whether the animal is exposed before or after the infection, and whether the infection is skin-associated or systemic.
Irradiation of skin by ultraviolet radiation in mice and humans leads to a suppression of cell-mediated immunity. This process is initiated when one of the photoreceptors in skin, trans-urocanic acid, is photoisomerized to cis-urocanic acid, an immunomodulator. High levels of L-histidine, histamine, and trans-urocanic acid are found in humans and animals when they are protein malnourished. Mice fed on an elevated L-histidine diet have more trans-urocanic acid in the skin and are more susceptible to UV-induced immune suppression. Sojourners to high altitudes are malnourished, suffer protein catabolism, are exposed to sun, and often acquire infectious diseases. There is evidence that sunscreens may not adequately protect the immune system. Furthermore, UV intensity increases with altitude. We propose a testable hypothesis: UV radiation causes photoimmune suppression in sojourners to high altitude and this allows infectious diseases to develop. The mechanism we propose includes protein malnutrition, high levels of trans-urocanic acid, ultraviolet radiation, formation of cis-urocanic acid, immune suppression, and infection.
The effects of short-term exposure to ultraviolet B (UVB) radiation on lymphocyte-related parameters were studied under controlled laboratory conditions using roach (Rutilus rutilus), a cyprinid teleost, as the model fish. In vitro lymphoproliferative responses stimulated with a T-cell-specific mitogen, concanavalin A (ConA), or a B-cell-specific activator, lipopolysaccharide (LPS), were decreased in exposed fish. Also nonstimulated proliferation was lower than in unexposed fish. ConA-activated responses returned to normal levels within 7 days after exposure, but LPS-activated responses were reduced throughout the 14 day follow-up. The capability of UVB-exposed fish to produce an antibody response was studied by intraperitoneal immunization with bovine gamma-globulin (BGG). The concentration of anti-BGG antibodies in plasma as well as the number of anti-BGG-specific antibody-secreting cells in the spleen or blood were not decreased in fish exposed either to a single dose of UVB prior to immunization, or to single dose of UVB prior to immunization followed by three additional doses after immunization. Immunoglobulin M (IgM) production, when assayed as plasma IgM level or as the number of IgM-secreting cells in the spleen or blood, was not suppressed after exposure to UVB irradiation. These results indicate that a single dose of UVB or short-term exposure to UVB irradiation has no negative effects on IgM production or reactivity against antigen administered via the intraperitoneal route. However, the suppression of in vitro lymphoproliferative responses suggest that exposure to UVB has the potential to interfere with lymphocyte-related functions in fish.
Recent studies on the immunosuppressive effects of ultraviolet radiation (UVR) and the related resistance to infections in rodents and humans are presented. The waveband dependency of trans-to-cis isomerisation of urocanic acid in the stratum corneum and the role of DNA damage in UVR-induced erythema and immunosuppression were investigated to further elucidate the underlying mechanisms. Furthermore, human experimental studies on UVR-induced immunomodulation were performed. It appeared that the doses needed to suppress various immune parameters in humans (e.g. NK activity, contact hypersensitivity) were higher than those needed in experiments in rodents. Still, extrapolation of experimental animal data to the human situation showed that UVR may impair the resistance to different systemic infections at relevant outdoor doses. In observational human studies we aimed to substantiate the relevance of UVR for infections in humans. It was shown that sunny season was associated with a slightly retarded but clinically non-relevant antibody response to hepatitis B vaccination. Furthermore, sunny season appeared to be associated with a small decline in the number of CD4+ T-helper cells in a cohort of HIV-infected persons and a higher recurrence of herpes simplex and herpes zoster in a cohort of renal transplant recipients. However, in a study among young children a higher exposure to solar UVR was associated with a lower occurrence of upper respiratory tract symptoms. As disentangling the effects of UVR from other relevant factors is often impossible in observational studies, concise quantitative risk estimations for the human situation cannot be given at present.
Depletion of stratospheric ozone and changes in lifestyle lead to an increased exposure to ultraviolet (UV) wavebands, especially in the UVB region (280-320 nm). Besides the beneficial effects of UV exposure, such as vitamin D production, cosmetic tanning, and adaptation to solar UV, UV exposure can also have adverse consequences on human health, notably sunburn, skin cancer, and ocular damage. Over the last two and a half decades it has become evident that especially UVB exposure and to a lesser extent UVA modulates specific as well as nonspecific immune responses. Several reports have shown that this immunomodulation plays at least a partial role in the induction of skin cancer. In addition, UVB exposure has been demonstrated to impair resistance to some infections. On the other hand, immunomodulation resulting from UVB exposure might be physiologically important in inhibiting responses to neoantigens in the skin induced by UV exposure. In the last 20 years UV has been used frequently as an experimental tool to unravel immune responses-especially immune responses initiated in the skin (i.e., photoimmunology). In this review, the major mechanisms responsible for UV-induced immunomodulation and its consequences are summarized.
Based on the well-described excess of schizophrenia births in winter and spring, we hypothesised that individuals with schizophrenia (a) would be more likely to be born during periods of decreased perinatal sunshine, and (b) those born during periods of less sunshine would have an earlier age of first registration.
We undertook an ecological analysis of long-term trends in perinatal sunshine duration and schizophrenia birth rates based on two mental health registers (Queensland, Australia n=6630; The Netherlands n=24,474). For each of the 480 months between 1931 and 1970, the agreement between slopes of the trends in psychosis and long-term sunshine duration series were assessed. Age at first registration was assessed by quartiles of long-term trends in perinatal sunshine duration. Males and females were assessed separately.
Both the Dutch and Australian data showed a statistically significant association between falling long-term trends in sunshine duration around the time of birth and rising schizophrenia birth rates for males only. In both the Dutch and Australian data there were significant associations between earlier age of first registration and reduced long-term trends in sunshine duration around the time of birth for both males and females.
A measure of long-term trends in perinatal sunshine duration was associated with two epidemiological features of schizophrenia in two separate data sets. Exposures related to sunshine duration warrant further consideration in schizophrenia research.
Ultraviolet light exposure can impair immune responses that are not restricted to the exposed skin but is also found at other sites, i.e. systemic immunosuppression. Therefore, we investigated the UV-induced modulating effects on vaccination against hepatitis B in a mouse model. Two different mouse strains, BALB/c and C57B1/ 6, were vaccinated intramuscularly against hepatitis B. Mice were exposed to different doses of ultraviolet B (UVB) for five consecutive days on shaved back skin before the vaccination. Vaccination against hepatitis B induced cellular (delayed-type hypersensitivity [DTH] and lymphocyte stimulation test) as well as humoral immune responses in both mouse strains. The DTH responses in C57BB1/6 mice were statistically significantly higher compared with BALB/c mice. UVB exposure induced a dose-dependent suppression of cellular immunity in both strains of mice. C57B1/6 mice seemed to be more susceptible to this suppression. Anti-hepatitis B surface antibodies (total-Ig) were only marginally suppressed after UVB exposure. IgG2a and interferon-gamma levels, both indicators for Th1 immune response, were suppressed in both mouse strains after UVB exposure. In summary, UVB exposure induced a dose-dependent suppression of both cellular and humoral immune responses after hepatitis B vaccination, although the suppressive effects on humoral immunity were limited to IgG2a production. Susceptibility to UVB-induced immunomodulation depended on the strain of mice and their predilection for developing different T cell responses.
In view of the capacity of ultraviolet radiation (UVR) to induce suppression of various immunological parameters and to enhance the viral replication of HIV, we investigated whether seasonal influences on immunological parameters that are relevant for HIV infection could be identified. As the sunny season is associated with high levels of ambient UVR, a decline of immunological parameters and an increase of the HIV viral load during the summer months might ensue. We analysed the immunological data of the HIV-infected homosexual men who participated in the Amsterdam Cohort Study on HIV infection and AIDS (1984-1996; n = 556). The effect of season on the individual development of various immunological parameters in time was examined by means of a random effects model for repeated measurements. Lower levels in the mean number of CD4+ T cells and the mean CD4+/CD8+ ratio were found during summer and spring, respectively (P = 0.0001/0.0001). For the CD8+ T cells, high mean values were observed both in April and September (P = 0.0001). The highest T-cell reactivity values were found during the summer (P = 0.0001). No effect of season on the viral load was established. The seasonal effect on CD4+ T cells seemed to be more pronounced at a more advanced stage of the HIV infection. It is concluded that the lower CD4+ T-cell counts during summer support the notion that solar UVR may have a suppressive effect on the cellular immunity of HIV-infected persons. However, whether this observation can be attributed to the effect of ambient UVR solely is questionable, as the other immunological parameters follow different seasonal courses and other reports suggest that both internal and environmental factors influence immunological parameters.
We studied a group of HIV-infected homosexuals who participated in the Amsterdam Cohort Study on HIV and AIDS to investigate whether greater exposure to sunlight is associated with a less favorable course of some important immunological parameters. This was done because ultraviolet radiation (UVR) is potentially harmful to the cellular immunity and may enhance viral replication. The exposure to UVR was estimated by means of a 2-year retrospective questionnaire in 1997. Both a 2-year cumulative estimate and estimates by 3-monthly episodes were calculated. The associations with CD4+ T-cell count, CD4+/CD8+ T-cell ratio, and T-cell reactivity were investigated. First, the associations between the cumulative estimate and the individual slopes of these parameters during the 2 years covered by the questionnaire were explored by means of a robust regression analysis. Secondly, the short-term association with the estimate by episode was examined by means of a linear mixed-effect model for repeated measurements (LME). No statistically significant associations with the cumulative estimate were found. Although a trend to lower values of the immunological parameters studied after short-term greater exposure in the LME model was observed, the differences were not statistically significant either. These findings suggest that exposure to sunlight does not have a suppressive effect on the above mentioned immunological parameters in HIV-infected persons.
Studies have been carried out to synthesize and characterize the photoconjugate between positively charged amino acid, arginine and DNA fragments and their role in the induction of anti-DNA antibodies.
Calf thymus DNA fragments of about 200 base pairs (bp) were covalently crosslinked with arginine under UV light. The amino acid was found to be covalently photoconjugated to DNA and resulted in the formation of a crosslink. The photoadduct was characterized by various physicochemical methods.
Photoaddition of arginine to 200 bp DNA rendered the nucleic acid conformer thermodynamically more stable than the native form. After systematic characterization of the photoadduct, it was used as an antigen for the generation of antibodies in experimental animals. The photoadducts were found to be immunogenic in rabbits, inducing high titre antibodies. The DNA-arginine photoadduct showed higher binding with SLE sera known to have high level of anti-DNA antibodies.
Naturally occurring anti-DNA autoantibodies were found to recognize DNA-arginine photoadduct. The recognition of DNA-arginine photoadduct by anti-DNA autoantibodies points to the role of modified DNA in the induction of anti-DNA antibodies in autoimmune disorders.
Exposing the skin of mice to UV radiation interferes with the induction of delayed and contact hypersensitivity immune responses initiated at nonirradiated sites. The identity of the molecular target in the skin for these immunosuppressive effects of UV radiation remains controversial. To test the hypothesis that DNA is the target for UV-induced systemic immunosuppression, we exposed C3H mice to UV radiation and then used liposomes to deliver a dimer-specific excision repair enzyme into the epidermis in situ. The application of T4 endonuclease V encapsulated in liposomes to UV-irradiated mouse skin decreased the number of cyclobutane pyrimidine dimers in the epidermis and prevented suppression of both delayed and contact hypersensitivity responses. Moreover, the formation of suppressor lymphoid cells was inhibited. Control, heat-inactivated endonuclease encapsulated in liposomes had no effect. These studies demonstrate that DNA is the major target of UV radiation in the generation of systemic immunosuppression and suggest that the primary molecular event mediating these types of immunosuppression by UV radiation is the formation of pyrimidine dimers. Furthermore, they illustrate that the delivery of lesion-specific DNA repair enzymes to living skin after UV irradiation is an effective tool for restoring immune function and suggest that this approach may be broadly applicable to preventing other alterations caused by DNA damage.
UV irradiation of mice causes a systemic immune alteration that can be detected either by suppression of the immunologic rejection of UV-induced tumors, or by suppression of contact hypersensitivity (CHS). Suppression of these two immunologic responses has similar photobiologic characteristics and in both cases is associated with the generation of antigen-specific suppressor T cells. To identify whether a specific photoreceptor for this effect exists, the relative wavelength effectiveness (action spectrum) was determined for the UV-induced suppression of CHS. Narrow bands of UV (half bandwidth 3 nm) were used at 10 wavelengths from 250 to 320 nm to obtain dose-response curves. Irradiation with each of these bands of UV caused dose-dependent immunosuppression of CHS, but with differing effectiveness. Immunosuppression was clearly separable from the generation of gross skin damage and inflammation. Further, immunosuppression by the most effective wavelength (270 nm) was associated with the generation of antigen-specific suppressor cells. The action spectrum derived from the dose-response curves has a maximum between 260 and 270 nm, a shoulder at 280-290 nm, and declines steadily to approximately 3% of maximum at 320 nm. The finding of such a clearly defined wavelength dependence implies the presence of a specific photoreceptor for this effect. Removing the stratum corneum by tape stripping before UV irradiation prevented the suppression of CHS using 254-nm radiation, suggesting the photoreceptor is superficially located in the skin. A number of epidermal compounds with absorption spectra similar to the action spectrum are discussed and evaluated with respect to their potential for being the photoreceptor. Based on (a) the close fit of its absorption spectrum to the action spectrum, (b) its superficial location in the stratum corneum, and (c) its photochemical properties, the hypothesis is advanced that the photoreceptor for systemic UV-induced immunosuppression of contact hypersensitivity may be urocanic acid. As such, it may also play a role in UV-induced carcinogenesis via the production of tumor-specific suppressor cells.
Urocanic acid (UCA) occurs naturally in the stratum corneum of the skin as the trans-isomer and, upon exposure to UVB radiation, converts to cis-UCA. It has been proposed that trans-UCA is the photoreceptor for and, following its isomerization to cis-UCA, a mediator of the suppressive effects of UVB irradiation on systemic T cell-mediated immune responses, such as contact hypersensitivity (CH) and delayed-type hypersensitivity (DTH). To address this question directly, we studied the consequence of deleting the in vivo function of cis-UCA on systemic suppression of CH and DTH, by injecting mice with a anti-cis-UCA mAb several hours before exposure to UVB radiation. We found that while DTH responses were completely restored, the anti-cis-UCA Ab had no effect on UV-induced immunosuppression of the CH response, even though suppressor cell formation was inhibited in both cases. Further, the kinetics of IL-10 expression in the skin of irradiated mice injected with the anti-cis-UCA mAb was altered and the diminished APC function of spleen-adherent cells from UVB-irradiated mice was totally reversed by the Ab. These findings suggest that cis-UCA acts as a mediator for some but not all of the systemic suppressive effects of UVB irradiation. They also suggest that cis-UCA may act indirectly via IL-10 to modulate immune function.
We have recently demonstrated that a single dose (200 J/m2) of UVB radiation abrogates the capacity of mouse epidermal Langerhans cells (LC) or splenic adherent cells (SAC) to present keyhole limpet hemocyanin (KLH) to Ag-specific, MHC-restricted CD4+ Th1 cells. In the present study we determined whether such Th1 unresponsiveness represented long-lasting immunologic tolerance. To address this question, Th1 were preincubated with KLH-pulsed UVB-LC or UVB-SAC, then isolated and restimulated with unirradiated APC (LC or SAC) plus KLH or with exogenous rIL-2 in the absence of APC. Preincubation with KLH and UVB-LC or UVB-SAC rendered Th1 unresponsive to subsequent restimulation with APC and KLH. In addition, such Th1 were defective in their autocrine IL-2 production, but could respond normally to exogenous rIL-2, indicating that unresponsiveness was due to functional inactivation and not to cell death. Th1 unresponsiveness was Ag-specific, MHC-restricted, and long lasting (greater than 16 days). In addition, it appears that Th1 unresponsiveness is not due to the release of soluble suppressor factors from UVB-LC or UVB-SAC because supernatants from such cells had no effect on Th1 proliferation. Addition of unirradiated allogeneic SAC during preincubation prevented the induction of unresponsiveness by UVB-LC or UVB-SAC, suggesting that UVB interferes with the capacity of LC or SAC to deliver a costimulatory signal(s) that can be provided by allogeneic SAC. We conclude that UVB can convert LC or SAC from immunogenic to tolerogenic APC.
In four different systems it was shown that murine delayed-type hypersensitivity (DTH) responses at 18-48 h were preceded by early 2-h responses. CBA mice immunized with picryl chloride, BDF1 mice immunized with oxazolone, BALB/c mice immunized with dinitrofluorobenzene, and C57BL/6 mice immunized with L5178Y lymphoma cells, and challenged with the appropriate specific antigen, all gave rise to expected 18-48 h delayed-in-time hypersensitivity reactions, but all of these responses were preceded by early hypersensitivity reactions that peaked at 2 h. These early 2-h reactions are transferable with T cells or with a T cell-derived, antigen-binding factor and are antigen-specific. The early and late components of DTH reactions are mast cell dependent since neither are elicited in mast cell deficient W/Wv or Sl/Sld mice. The T cell activity mediating the early component of DTH is demonstrable as early as 24 h after immunization, while the classical late component of DTH is not demonstrable until days 3-4. The difference in onset after immunization of the early and late components of DTH, and the different kinetics of these components in recipients of cell transfers that were challenged immediately or 24 h after transfer, led to the hypothesis that immunization for DTH leads to rapid induction in lymphoid organs of a certain population of T cells to produce an antigen-binding factor. This factor sensitizes peripheral tissues, probably mast cells, and local challenge with appropriate antigen leads to mast cell activation and release of the vasoactive amine serotonin, resulting in increased permeability of the local vasculature. This allows other circulating antigen-specific T cells, which are induced later after immunization, to enter the tissues and interact with antigen, resulting in production of chemoattractant lymphokines that recruit accessory leukocytes such as monocytes and polymorphs to enter the tissues via gaps between endothelial cells. These inflammatory cells, that are recruited to the site via two different T cell activities, constitute the characteristic infiltrate of DTH responses. Identification of an early 2-h component of DTH that is T cell- and mast cell-dependent provides evidence that the tissue-sensitizing, antigen-binding, T cell factor probably functions in vivo in the early phases of DTH responses.
Two types of antigen-specific T cells are needed for the elicitation of contact hypersensitivity reactions. They act in an obligate sequence to mediate the early initiating and late effector phases of contact hypersensitivity, which are accompanied by skin-swelling responses at 2 and 24 h after challenge, respectively. The magnitude of the late ear swelling depends on that of the early swelling.
We studied the influence of ultraviolet radiation on both phases of contact hypersensitivity to picrylchloride. Mice were exposed to subedemal doses of ultraviolet radiation on the shaved backs for four consecutive days. Four days later mice were sensitized on non-irradiated skin. Four days after sensitization mice were challenged on the ears, and swelling was measured 2, 4, and 24 h after challenge. The early and late phases of contact hypersensitivity were largely suppressed in ultraviolet-irradiated, actively sensitized mice. Transfer of immune lymphoid cells from donor mice that were sensitized 4 d earlier induced early and late components of contact hypersensitivity in naive recipients after challenge. Transfer of immune lymphoid cells from donors that were sensitized 1 d earlier only induced the early component of contact hypersensitivity. Ultraviolet irradiation of donor mice significantly reduced the capacity of the immune lymphoid cells to induce contact hypersensitivity. We show that lymphoid cells responsible for the early and late components of contact hypersensitivity are both affected.
Abstract— C3H mice were irradiated three times a week for up to 6 weeks with either 500 J/m2 or 1000 J/m2 broadband UVB (270–350 nm) or 3000 J/m2 narrowband UVB (311–312 nm; TL01 source). Each dose was suberythemal to the mouse strain used. The number of Langerhans cells (LC) in the epidermis was reduced by over 50% after 2 weeks of irradiation with the UVB source and by 20% following TL01 irradiation. Continued irradiation for up to 6 weeks resulted in no further decrease in LC numbers in the case of the UVB source but a steady decline to 40% in the case of the TL01 source. Sunburn cells were detected following irradiation with both sources but the numbers were very low in comparison with acute exposure. Ultraviolet-B exposure resulted in doubling of the thickness of the epidermis throughout the 6 weeks of irradiation while TL01 exposure did not alter epidermal thickness. Conversion of trans- to ew-urocanic acid (UCA) was observed with both UVB and TL01 sources. The percentage of cis-UCA started to return to normal after 4 weeks of TL01 exposure despite continued irradiation. As observed following a single exposure, the contact hypersensitivity (CH) response was significantly reduced following 6 weeks of UVB irradiation but was unaffected by TL01 exposure, indicating no correlation between cis-UCA levels and CH response. Total serum immunoglobulin levels remained unchanged throughout the 6 weeks of UVB or TL01 irradiation but IgE titers significantly increased in all cases in the first 2 weeks of irradiation, indicating a possible shift to a TH2 cytokine profile. The IgE levels started to return to normal at later times. Thus chronic broadband UVB exposure induces a number of cutaneous and systemic responses that are likely to be dose dependent, while chronic TL0I exposure induces only some of the these responses.
Trans to cis photoisomerization of epidermal urocanic acid (UCA) has been proposed as a primary event in UV-induced immunosuppression. 8-Methoxypsoralen (8-MOP) in combination with UVA radiation (PUVA) is used for photochemotherapy of several immunologicaly based skin disorders, and PUVA is known to cause immunosuppression. We examined the photointeraction of 8-MOP and other skin photosensitizing drugs (amiodarone, ciprofloxacin, doxycycline and ketoprofen) with trans-UCA in vitro. In oxic condition 8-MOP did not enhance the ability of radiation from standard PUVA fluorescent sources (0.2% radiation below 320 nm) to produce cis-UCA. When oxygen was removed, some 8-MOP photosensitization could be detected. 8-MOP, ciprofloxacin and ketoprofen also enhanced inefficient UCA photoisomerization by radiation from a filtered tungsten halogen source (0.2% radiation below 320 nm). 8-MOP photosensitization is essential for radiation from PUVA tubes to have a therapeutic or immunosuppressive effect. We have shown in vitro that 8-MOP does not enhance cis-UCA production by this source. Extrapolation of our data to the in vivo situation suggests that UCA may not be involved in either the therapeutic or the immunosuppressive effect of PUVA.
Thesis--Universiteit Utrecht, 1995. Includes bibliographical references. "Effecten van UV-B straling op de weerstand tegen infectieziekten"--Dutch title. "Effect of ultraviolet-b radiation on the resistance to infectious diseases"--Cover title. "UVB radiation and resistance to infectious diseases."--Spine title.
Previously it has been shown that ultraviolet-B (UVB) irradiation or cis-urocanic acid (cis-UCA) treatment of mice before infection with herpes simplex virus (HSV) suppressed the delayed hypersensitivity (DH) response when the mice were subsequently challenged with inactivated virus. In the present study, the time course of the elicitation phase of the DH was examined, and it was found to be biphasic with one peak 1 h following challenge and a second at 24 h. Both UVB irradiation and cis-UCA treatment of mice before infection with HSV significantly suppressed the DH at 1 h as well as at 24 h. The role of tumour necrosis factor-alpha (TNF-alpha) in the suppression was tested by injecting mice intraperitoneally with neutralizing TNF-alpha antibodies 2 h before UVB irradiation or cis-UCA treatment followed by infection with HSV. This had no effect on the suppression of DH to HSV induced by cis-UCA but significantly reduced that generated by UVB exposure. Thus, the mechanism of suppression of DH induced by UVB irradiation or cis-UCA may be different.
We have recently demonstrated that a single dose (200 J/m2) of UVB radiation abrogates the capacity of mouse epidermal Langerhans cells (LC) or splenic adherent cells (SAC) to present keyhole limpet hemocyanin (KLH) to Ag-specific, MHC-restricted CD4+ Th1 cells. In the present study we determined whether such Th1 unresponsiveness represented long-lasting immunologic tolerance. To address this question, Th1 were preincubated with KLH-pulsed UVB-LC or UVB-SAC, then isolated and restimulated with unirradiated APC (LC or SAC) plus KLH or with exogenous rIL-2 in the absence of APC. Preincubation with KLH and UVB-LC or UVB-SAC rendered Th1 unresponsive to subsequent restimulation with APC and KLH. In addition, such Th1 were defective in their autocrine IL-2 production, but could respond normally to exogenous rIL-2, indicating that unresponsiveness was due to functional inactivation and not to cell death. Th1 unresponsiveness was Ag-specific, MHC-restricted, and long lasting (greater than 16 days). In addition, it appears that Th1 unresponsiveness is not due to the release of soluble suppressor factors from UVB-LC or UVB-SAC because supernatants from such cells had no effect on Th1 proliferation. Addition of unirradiated allogeneic SAC during preincubation prevented the induction of unresponsiveness by UVB-LC or UVB-SAC, suggesting that UVB interferes with the capacity of LC or SAC to deliver a costimulatory signal(s) that can be provided by allogeneic SAC. We conclude that UVB can convert LC or SAC from immunogenic to tolerogenic APC.
Using information on solar irradiance at different latitudes derived from a radiative transfer model and a detailed in vivo action spectrum for immune suppression in a murine system, we report here calculations of the "biologically effective" irradiance of sunlight for immune suppression. From 40 degrees N to 40 degrees S in summer, under normal stratospheric ozone concentrations this value ranged from 0.27 W/m2 (40 degrees N or S) to a peak of 0.33 W/m2 (20 degrees N or S) predicting that 50% immune suppression in the Balb/c mouse would occur after 21-26 min of sunlight exposure within this latitude range. We also found that the most effective wavelengths for immune suppression shift from a peak of 270 nm in the laboratory to near 315 nm in sunlight. Furthermore, using ozone depletion scenarios of 5 to 20%, at latitudes 20 degrees S and 40 degrees N, a 0.6% increase in biologically effective irradiance levels of solar UVB for immune suppression was predicted for each 1% decrease of ozone. This value rose to a nearly 1% increase for each 1% decrease in ozone at 60 degrees N latitude in wintertime. These data indicate that activation of immune suppression, in a murine model, requires relatively low levels of sunlight and that these levels are easily obtainable over most of the populated regions of the world. Since a UVB-activated photoreceptor, urocanic acid, regulates immune suppression in mice and since this same compound exists on other mammalian skin, including human skin, suppression of the mammalian immune system is predicted to increase if substantial stratospheric ozone depletion takes place.
The exposure of experimental animals to the inflammatory effects of ultraviolet radiation (UVR) is known to cause depressions in their ability to initiate and effectuate various types of cellular immune responses. Contact-type and delayed-type hypersensitivity, plus the ability to generate protective forms of anti-viral and anti-tumor immunity, are all affected by the prior exposure of normal animals to the effects of this physical agent. Presently, the cellular and molecular mechanism(s) responsible for mediating the changes in immune function observed in UVR-exposed animals is not fully understood. Herein we report that one reproducible consequence of exposing normal mice to low doses of UVR is a dramatic change in the pattern of lymphokines secreted by their activated T cells. Lymphocytes isolated from UVR-exposed donors produce/secrete greatly reduced levels of the T cell lymphokines IL-2 and IFN-gamma activation in vitro with protein Ag of the polyclonal T cell stimulant anti-CD3. The secretion of IL-4 by these lymphocyte cultures, however, is consistently elevated in comparison to normal controls. Further studies determined that a similar change in lymphokine production was induced when mice were treated with either bacterial LPS or rIL-1 beta, a cytokine known to be elevated in vivo after UVR or LPS exposure. The ability of IL-1 to facilitate a change in the capacity of T lymphocytes to produce/secrete lymphokines after in vitro activation does not appear to represent a direct effect of this cytokine on lymphocyte or accessory cell targets because addition of IL-1 beta to cultures of Ag-primed lymphocytes obtained from normal donors was incapable of altering the pattern of lymphokine production. Collectively, our present results add further support to the hypothesis that UVR-induced elevations in endogenous IL-1 are, in part, responsible for the immunomodulatory effects of UVR. These findings provide compelling evidence that UVR, plus other agents capable of endogenously stimulating the production of IL-1, may function to alter the expression of different effector mechanisms in vivo. This could be facilitated through selective reductions in lymphokines produced by Th-1-type cells (IL-2 and IFN-gamma) and a simultaneous augmentation in a lymphokine produced by Th-2-type cells (IL-4).
— A hybrid cell line (hybridoma) has been isolated after fusion between mouse-plasmacytoma cells and spleen cells from mice immunized with a thymine dimer-containing tetranucleotide coupled to a carrier protein. Monoclonal antibodies produced by this hybridoma were characterized by testing the effect of various inhibitors in a competitive enzyme-linked immunosorbent assay (ELISA). The antibodies have a high specificity for thymine dimers in single-stranded DNA or poly(dT), but do not bind UV-irradiated d(TpC)5. Less binding is observed with short thymine dimer-containing sequences. In vitro treatment of UV-irradiated DNA with photoreactivating enzyme in the presence of light, or with Micrococcus luteus UV-endonuclease results in disappearance of antigenicity. Antibody-binding to DNA isolated from UV-irradiated human fibroblasts (at 254 nm) is linear with dose. Removal of thymine dimers in these cells during a post-irradiation incubation, as detected with the antibodies, is fast initially but the rate rapidly decreases (about 50% residual dimers at 20 h after 10 J/m2). The induction of thymine dimers in human skin irradiated with low doses of UV-B, too, was demonstrated immunochemically, by ELISA as well as by quantitative immunofluorescence microscopy.
-The acute effects of low-fluence ultraviolet light, primarily between wavelengths 280 and 320 nm (ultraviolet B) on T-lymphocyte subsets were assessed in virro and in vivo by quantitative cytofluorometric analysis. In virro, 90J/m2 of ultraviolet irradiation of human mononuclear cells produced a significant increase in the OKT4 (helper-inducer)/OKT8 (suppressor-cytotoxic) ratio (P>0.008), due primarily to a decrease in the OKT8 subset. In vivo, 24 h after whole-body UV irradiation of human subjects with one half of a minimal erythemal dose of ultraviolet B the OKT4/OKT8 ratios again increased (P > 0.002), again with somewhat greater effects on the OKT8 subset. These results indicate that suberythemal exposure to UV light increases OKT4/OKT8 ratios in normal human subjects because of differential effects on lymphocyte subsets. They suggest that casual exposure to sunlight mediates immunologic changes in normal human subjects.
Ultraviolet B (UVB) radiation is reported to induce a defect in epidermal antigen presentation which leads to specific suppression of the delayed-type hypersensitivity (DTH) response to trinitrochlorobenzene. We have used a similar system to examine the murine DTH response to herpes simplex virus type 1 (HSV-1). Mice irradiated with 96 mJ/cm2 UVB on shaved dorsal skin 3 days before s.c. injection of live HSV-1 in the flank showed 54-92% suppressed DTH responses to challenge with inactivated virus compared with nonirradiated control animals. If irradiation took place 7 days before inoculation with virus, some suppression of DTH occurred; if 14 days before, no suppression was found. The transient nature of the UVB response is further illustrated by the observation that irradiation with the same dose of UVB 5 h before, or 3 days after, inoculation with virus had no effect on DTH. Once induced, some degree of UVB suppression was found to persist for at least 3 months after irradiation.
The effects of exposure to natural sunlight on the immune system were studied in 15 normal human subjects. Exposure was for 1 hr each day for 12 days over 2 wk and tests were carried out before, on completion, and 2 wk after completion. In comparison to concurrent studies on 13 age- and sex-matched controls, sun-exposed subjects had a significant increase in their circulation of T cells recognized by OKT8 monoclonal antibodies and a decrease in OKT4 positive T cells. Suppressor T cell activity measured in pokeweed mitogen-stimulated cultures of T and B cells was significantly increased against IgG and IgM production. These changes were still evident in many of the subjects 2 weeks after completion of the sun exposure. A trend for depression of natural killer cell activity against a melanoma target cell was noted in the present study, but this did not appear as marked as that noted previously in subjects exposed to radiation in solariums. The differences between the effect of radiation from solariums and natural sunlight on the immune system may result from the higher dosage of UV-A in radiation from solariums. The results suggest that exposure to sunlight may favor the induction of suppressor pathways in response to antigenic stimuli and that this may limit immune responses against tumor cells such as melanoma. They support the idea from animal studies that systemic changes in the immune system may be an important factor in the association of UV radiation with malignancy.
E-Urocanic acid exhibits a single, featureless, long-wavelength absorption band with λmax˜258 nm in water. However, the quantum efficiency for E→Z photoisomerization is wavelength dependent in this region, with the maximum value at the low energy edge of the band (e.g. 313 nm) and appreciably lower efficiencies measured at ≦ 300 nm.
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.
Ultraviolet B (UVB) irradiation of C3H mice causes suppression of delayed hypersensitivity and contact hypersensitivity (CH) to antigens encountered following exposure, and is accompanied by a reduction in Langerhans cell (LC) numbers in the epidermis, loss of epidermal antigen-presenting cell function, and accumulation of dendritic cells in lymph nodes draining the site of irradiation. Various photoreceptors and mediators of these changes have been proposed, one of which is cis-urocanic acid (cis-UCA) formed from the naturally occurring trans-UCA in the epidermis on UV irradiation. A monoclonal antibody that reacts with cis-UCA has become available recently and has been used in this study to clarify the role of UCA. Pretreatment of C3H mice with the monoclonal antibody abrogated the UVB-induced and cis-UCA-induced reduction in epidermal LC numbers. It also prevented the UV-induced suppression of epidermal antigen-presenting cell ability as measured by the mixed skin lymphocyte response. However, it had no effect on the accumulation of dendritic cells in lymph nodes draining the site of UV exposure. With regard to hypersensitivity responses, it did not prevent UV-induced suppression of CH to oxazolone at a range of concentrations but it restored to normal the UV-suppressed delayed hypersensitivity to herpes simplex virus, if administered before exposure. Thus cis-UCA is involved in some UV-induced changes in murine skin but not in others, where alternative mediators, such as tumor necrosis factor-alpha, may be more important.
Ultraviolet radiation is absorbed in the skin, especially in the epidermis. After ultraviolet irradiation the number of major histocompatibility complex class II+, adenosine triphosphatase+ Langerhans cells and Thy-1+ dendritic epidermal cells in the epidermis decreases. Whether this decrease is due to migration of these cells or to loss of membrane markers is not clear. To address this question we have used the monoclonal antibody H3 directed against cyclobutyl thymine dimers-a form of DNA damage that is specifically induced by ultraviolet radiation-to investigate whether H3+ cells are present in the draining lymph nodes of the skin after ultraviolet irradiation of hairless, inbred mice (HRA/Skh). After a single dose of ultraviolet radiation (Westinghouse FS40, 1.5 kJ/m2), H3+ cells were present in the paracortex of the draining lymph nodes. No positive cells were found in the blood of irradiated mice. These results suggest that the H3+ cells in the lymph nodes originate from the skin. The number of H3+ cells in the draining lymph nodes increased the first 24 h after irradiation and then stabilized. Immunohistochemical double staining revealed that all H3+ cells were major histocompatibility complex II+, and that only a fraction of the cells were NLDC-145 positive. No V gamma 3 T-cell receptor bearing cells could be found in the lymph nodes after UV irradiation of the skin.
A rat cytomegalovirus infection model for use in immunotoxicity testing has been developed. In resistance against viruses, natural killer cells and cytotoxic T-cells play an important role. Therefore, this model complements other rat host resistance models for immunotoxicity testing, i.e. existing bacterial and parasitic infection models in which cytotoxic T-cells and natural killer cells play a minor role. Host resistance against cytomegalovirus infections in the rat was determined by titrating infectious virus levels in organs after cytomegalovirus infection in an in vitro infectivity test denoted as the Plaque Forming Unit (PFU) Test. In this test, homogenates of different organs were investigated for infectious virus titers on rat embryonic cell monolayers. We demonstrated that in the salivary gland, the major target organ for rat cytomegalovirus, virus was detectable from 8 days onward after intraperitoneal infection. To show that this model is suitable for the detection of immunotoxicity four different methods for immunosuppression were investigated: 1. gamma-irradiation, 2. congenitally athymic rats, 3. chemically induced immunosuppression, 4. ultraviolet-B (UVB) irradiation. Rat cytomegalovirus titers in the salivary glands of irradiated (500 rad 1 day prior to infection) or congenitally athymic rats were significantly increased as compared to non-irradiated rats and euthymic control rats respectively. In TOX-Wistar rats, given 20 or 80 mg bis(tri-n-butyltin)oxide (TBTO) per kg food beginning 6 weeks before cytomegalovirus infection, a regimen known to have immunotoxic effects, cytomegalovirus titers in the salivary glands were significantly increased as compared to non-TBTO-treated cytomegalovirus infected rats.(ABSTRACT TRUNCATED AT 250 WORDS)
Having previously shown in vitro that ultraviolet B (UVB)-treated Langerhans cells (LC) can induce antigen-specific proliferative unresponsiveness and tolerance in Th1 (but not Th2) cells, we wanted to determine whether cutaneous exposure to UVB radiation prior to hapten-painting would produce similar differential effects in hapten-reactive Th1 and Th2 T cells in vivo. C3H/HeN mice were exposed to UVB (200 J/m2/day) through abdominal skin on days -4 through -1, followed by painting dinitrofluorobenzene (DNFB) on the irradiated skin on days -1 and 0. Induction of allergic contact sensitivity (CS) was assayed by ear swelling responses to DNFB and by the proliferative responses of draining lymph node cells (LNC) to DNBS. UVB-irradiated and hapten-painted mice (in comparison to a control panel of unirradiated and DNFB-painted mice) displayed suppressed ear swelling responses to DNFB and suppressed LNC proliferation to DNBS. However, LNC from either panel of mice proliferated well in response to exogenous interleukin 2 (IL-2). To examine effects on Th1 and Th2 cells, lymphokines were assayed from supernatants of DNBS-stimulated LNC. The Th1-associated lymphokines, interferon-gamma and IL-2, were the predominant cytokines detected in samples taken from unirradiated and DNFB-painted mice. Both of these cytokines were reduced markedly in samples from UVB-treated and DNFB-painted mice. Except for miniscule amounts of IL-10, no Th2-associated lymphokines were detected in LNC supernatants from either panel of mice. These results suggest that UVB-induced suppression of CS in vivo is associated with functional inactivation of hapten-reactive Th1 cells.
Although broadband UV-B irradiation has been shown to induce selective immunosuppression in a variety of experimental systems, the wavelength dependence of the immunomodulation and the initial events in the skin remain unclear. In the present study three UV lamps were used at suberythermal doses on C3H mice: a conventional broadband UV-B source (270-350 nm), a narrowband UV-B source (311-312 nm) and a UV-A source (320-400 nm). Their effects on the photoisomerization of the naturally occurring trans-isomer of urocanic acid (UCA) to cis-UCA, on the density of Langerhans cells and on the ability of epidermal cells to stimulate allogeneic lymphocytes in the mixed skin lymphocyte reaction (MSLR) were ascertained. Broadband UV-B irradiation was more efficient than narrowband UV-B at reducing the density and function of Langerhans cells, while UV-A irradiation was least effective. These changes were most pronounced immediately following irradiation, were dose dependent and were only detected in UV-exposed areas of skin. There was a close correlation between the UV-induced reduction in Langerhans cell density and the formation of cis-UCA in the epidermis. This correlation was not detected between the reduction in the MSLR response following UV irradiation in vivo and cis-UCA formation.
In this study lymphocytes from blood and/or spleen of different species (rat, mouse, human) were exposed to different doses of ultraviolet radiation (UVR). The functional activity of these lymphocytes was determined using assays for mitogen proliferation and the mixed lymphocyte response (MLR). These experiments demonstrated that in vitro exposure to UVR causes a dose-dependent decrease of the MLR activity of the irradiated lymphocytes. Viability of lymphocytes and mitogen proliferation responses were also decreased by UVR exposure but less severe in comparison to the MLR. Lymphocytes of rats seem to be more sensitive to UVR as compared to lymphocytes of mice and humans.
Exposure to ultraviolet radiation is associated with the development of cutaneous carcinomas, and with suppression of immune responses to a variety of antigens, including those of fungal, bacterial and parasitic origin, and contact sensitizers. UV irradiation also influences viral infections. It can affect viral mutation, the photolocalization of viral exanthems, viral oncogenesis, activation of viral genomes, and the suppression of immune responses to viruses. The evidence for, and mechanisms involved in, each of these categories is presented, and the effect of UV radiation on the virus-host interaction, particularly during persistent infections, is discussed.
It is known that ultraviolet-B light (UV-B) affects human health. In addition to deleterious effects on the skin and the eyes, such as erythema, photoageing, keratitis and cataract, UV-B is also able to impair the resistance against skin-associated tumours and infections. Our data implicate that UV-B can impair the resistance against certain non-skin-associated infections in rats, such as Listeria monocytogenes, Trichinella spiralis and Ratcytomegalovirus (RCMV). Rats, infected with T. spiralis, had an increased amount of T. spiralis larvae in their carcasses after UV-B exposure in comparison to control animals, indicating that the resistance to this parasite was decreased by UV-B. Exposure to UV-B caused an increase of RCMV load in the salivary gland 26 days after infection with this virus, indicating that especially the resistance against the second generation of viruses was impaired. In L. monocytogenes-infected rats, UV-B exposure caused an increased number of bacteria in the spleen, coupled to a decreased specific response of T lymphocytes to the bacteria. We conclude that UV-B radiation may affect the resistance against several non-skin-associated infectious diseases, which is probably caused by a defect in the specific lymphocyte response to the antigen.
Ultraviolet (UV) radiation suppresses a variety of immune responses but it is uncertain whether this action contributes to the effectiveness of phototherapy. Urocanic acid (UCA) has been proposed as a mediator of the immunologic effects of UV. On exposure the naturally occurring trans-isomer of UCA in the skin changes into the cis-isomer, which has been demonstrated to mimic many of the immunomodulatory effects of UV irradiation. Natural killer (NK) cells play an important role in several immunologic processes and published evidence indicates that their activity is altered by UV irradiation. To ascertain the effect on NK cells of phototherapy used in the treatment of psoriasis, modulation of NK activity in psoriatic patients undergoing broad-band UVB, narrow-band UVB, or psoralen plus (PUVA) regimens was examined. This was compared with NK cell activity in psoriatic patients treated with topical coal tar and in normal subjects receiving broad band UVB. The NK cell activity of psoriatic and normal subjects was the same over a wide range of effector to target cell ratios. Almost all patients undergoing phototherapy exhibited depressed NK cell activity during or after irradiation, although the timing of the depression varied between the lamps used and may be related to dose. However, patients treated with topical coal tar showed unchanged NK cell activity throughout the therapy. The effect of UCA isomers on NK cell activity in vitro was also determined. It was found that cis-UCA induced a dose-dependent suppression of NK cell activity in both patients and normal subjects, whereas trans-UCA had hardly any effect in either group. Thus it is possible that there may be a correlation between cis-UCA formation in the epidermis and the modulation of NK cell activity that occurs during phototherapy.
Ultraviolet radiation (UVR) is known to suppress some cell-mediated immune responses to antigens encountered during or soon after exposure. Phototherapy is widely used in psoriasis, and this study was undertaken to monitor changes in a range of immunological parameters during standard courses of treatment, with the aim of ascertaining whether such modulations contribute to the effectiveness of therapy. The responses of 17 patients with psoriasis undergoing UVB therapy, and four receiving PUVA therapy, were compared with 15 patients receiving coal tar treatment and four normal subjects undergoing UVB irradiation. In each case, samples were taken before starting therapy, after 4 weeks of therapy, and 4 weeks after completion of treatment. Serum immunoglobulin isotypes and complement components were within normal ranges in most of the psoriasis patients, and remained unchanged throughout therapy. Similarly, percentages of subsets of peripheral blood mononuclear cells (PBMC) were normal, and were unaltered by treatment. Patients who were already infected with herpes simplex virus (HSV), as demonstrated by a positive lymphoproliferation test in vitro, were monitored for asymptomatic HSV shedding and HSV recrudescences during therapy. There was little evidence that phototherapy caused reactivation of the virus. No significant alteration in lymphoproliferative response to HSV and to the mitogen concanavalin A was observed during therapy. Epidermal cells and blood adherent cells were used to present HSV to PBMC, depleted of adherent cells and enriched for T cells, in a lymphoproliferative assay. The functional antigen-presenting ability of adherent cells remained unchanged throughout therapy, whereas that of epidermal cells was suppressed during UVB irradiation and recovered, in most instances, after UVB therapy had been completed. The epidermis of patients with psoriasis contained about three times the quantity of urocanic acid (UCA) of normal subjects, whereas the UCA concentration in suction blister fluid did not differ between the two groups. During UVB irradiation, the percentage of cis-UCA rose in both the epidermis and suction blister fluid of all subjects, and it remained elevated in the blister fluid after therapy had finished. Tumour necrosis factor-alpha was measured in suction blister fluid, and its concentration did not alter consistently as a result of therapy. Whether any of the immunological parameters measured, and the changes noted, contribute to the effectiveness of phototherapy in the treatment of psoriasis remains uncertain.
Urocanic acid (UCA) is a major UV chromophore in the upper layers of the skin where it is found predominantly as the trans isomer. UV irradiation induces photoisomerisation of trans-UCA to cis-UCA which has been shown to mimic some of the immunosuppressive properties of UV exposure. We examined the wavelength dependence for trans-UCA to cis-UCA photoisomerisation in vitro and in mouse skin in vivo over the spectral range 270-340 nm. The resulting action spectra were very similar with maximal effectiveness at 300-315 nm and equal activity at 270 nm and 325-330 nm, demonstrating that UVA-II radiation (320-340 nm) is efficient at UCA photoisomerisation. These action spectra differed markedly from the trans-UCA absorption spectrum in vitro and also the reported action spectrum for UV suppression of contact hypersensitivity in mice. These findings suggest that the relationship between cis-UCA formation in skin and UV-induced immunosuppression may be complex.
Urocanic acid (UCA) is found in the stratum corneum as the trans-isomer and, on ultraviolet (UV) irradiation, photoisomerization into cis-UCA takes place. Cis-UCA has been suggested to play a part in UV-induced immunosuppression. In the present study, the concentration of UCA and the percentage as cis-UCA at 10 different body sites of 20 normal volunteers were analysed. A large interindividual variation in total UCA concentration was found, but the mean UCA concentration in each site was similar, other than at the sole of the foot. There was little variation in the UCA content between sites normally exposed, and not exposed, to light, but the percentage of UCA in the cis form was clearly higher at exposed areas.
Previous studies have indicated that suberythemal ultraviolet B (UV-B) irradiation of C3H mice before primary infection with herpes simplex virus (HSV) type 1 does not result in increased morbidity or mortality, but a suppressed delayed type hypersensitivity (DH) to the virus can be demonstrated. Any effect of UV radiation on pathogenesis during secondary epidermal HSV infection has not been previously examined. Mice were immunized by subcutaneous injection of inactivated HSV and, 5 days later, one group was UV-B-irradiated. The next day all mice were challenged epidermally with HSV. Most of the mice (92%) in the irradiated group developed severe lesions, whilst 59% of the non-irradiated group had mild lesions and 30% no lesions. Infectious virus was not isolated from the adrenal glands after challenge in either group. In addition, the DH to the virus was not affected by the UV exposure. The numbers of lymphocytes and dendritic cells in the lymph nodes draining the site of epidermal infection were increased in the UV group compared with the non-irradiated group. Following challenge, the percentage of CD4+ and CD8+ lymphocytes in lymph nodes was unaltered but the MHC class II expression on dendritic cells in these lymph nodes was reduced by UV exposure. The lymphoproliferative response in vitro of lymph node cells revealed a suppressed response to HSV and to the mitogen concanavalin A in the irradiated group. Thus, UV irradiation prior to epidermal secondary infection with HSV led to more severe infections due, perhaps, to a modulation in local antigen presentation.
A rat infection model using the bacterial pathogen Listeria monocytogenes was employed to analyze the immunosuppressive activity of UVB radiation. Rats were exposed to suberythemal doses of UVB radiation for 5 or 7 consecutive days, using Kromayer or FS40 lamps respectively. Subsequently, the rats were infected subcutaneously or intravenously with Listeria. Exposure to UVB resulted in an increased number of bacteria in the spleen 4 days after infection. Listeria-specific lymphocyte proliferation assays as well as delayed-type hypersensitivity reactions demonstrated that T cell-mediated immunity to Listeria was impaired by UVB as measured 4 and 8 days after infection. In addition, UVB exposure decreased phagocytotic activity of peripheral blood macrophages. This study demonstrated that suberythemal doses of UVB radiation caused a delay in the clearance of Listeria bacteria from the spleen of the rats and that this was probably caused by impaired nonspecific phagocytosis of Listeria by macrophages in addition to an impaired activity of Listeria-specific T cells.
The aim of this study was to develop a quantitative risk assessment of lowered resistance to infections in humans due to (solar) ultraviolet B (UVB) exposure. We followed the steps for risk assessment as defined by the U.S. National Academy of Sciences: (1) hazard identification, (2) dose-response assessment, (3) exposure assessment, and (4) risk characterization. For step 1, the suppressory effects of UVB radiation on the immune system have been reviewed, supplemented with new data, and analyzed. Experiments on UV-induced immunosuppression cannot be performed with humans for ethical reasons, but herpes simplex virus infection appears to be the human paradigm. Thus, UVB radiation appears to be a potential hazard to immunologic functions. Step 2 is crucial, but dose-response relationships for infections have never been measured in humans. We used our earlier dose-response rat data for suppression of lymphocyte stimulation and computed that the UVB dose resulting in a 50% reduction of lymphocyte stimulation by Listeria monocytogenes is 6.800 J/m2. Using mixed skin lymphocyte response assays we found that humans are 3.8 times less sensitive than rats (interspecies variation [IEV]). To account for the 2.5 percentile of most susceptible individuals in a population, an additional factor (intraspecies variation [IAV]) was introduced (0.5 for humans). Using these data, we computed that 13.100 J/m2 of UVB radiation emitted by FS40 lamps would suppress 50% of the proliferative response of lymphocytes to L. monocytogenes in most sensitive skin type 2 humans. In step 3, we assumed the action spectrum for the responses analyzed by us as identical to an action spectrum for suppression of contact hypersensitivity that is available in the literature. This led us to step 4, where we calculated that approximately 100 min of solar exposure at around noon in Italy or Spain would suppress the resistance to infections by L. monocytogenes in the most sensitive humans.
Orolabial human infections with herpes simplex virus type 1 (HSV-1) are very common; following the primary epidermal infection, the virus is retained in a latent form in the trigeminal ganglia from where it can reactivate and cause a recrudescent lesion. Recrudescences are triggered by various stimuli including exposure to sunlight. In this review three categories of mouse models are used to examine the effects of UV irradiation on HSV infections: these are UV exposure prior to primary infection, UV exposure as a triggering event for recrudescence and UV exposure prior to challenge with virus in mice already immunized to HSV. In each of these models immunosuppression occurs, which is manifest, in some instances, in increased morbidity or an increased rate of recrudescence. Where known, the immunological mechanisms involved in the models are summarized and their relevance to human infections considered.
Our laboratory has demonstrated in preliminary experiments that UVB exposure using the Kromayer lamp can induce increased numbers of Trichinella spiralis larvae in carcasses of infected Wistar rats, without affecting specific antibody titers to this parasite. In this study, orally T. spiralis-infected Wistar rats were exposed to suberythemal doses of UVB radiation using FS40 lamps during different time periods before or after infection. A significant increase in the number of T. spiralis larvae was found in the carcasses of rats that were UVB irradiated daily for 7 consecutive days in the second week after infection. Additionally, increased numbers of larvae were also detected histologically in the tongue of rats that were exposed the first and the second week after infection. Lymphocyte stimulation assays using mesenteral lymph node cells indicated that UVB exposure also impaired the specific lymphocyte response to T. spiralis. Moreover, DTH responses to T. spiralis were severely impaired in rats that were UVB irradiated daily for 7 consecutive days in the second week after infection. Thus, these data combined with the data of the Kromayer study indicate that exposure of rats to FS40 irradiation following oral infection with T. spiralis leads to increased numbers of larvae in systemic sites and impaired T-cell immunity to the parasite.
The numbers and function of circulating lymphocyte subsets are within normal ranges in patients with psoriasis and are not affected by 4 weeks of ultraviolet (UV) therapy, except for a suppression in natural killer (NK) cell activity. However, it is possible that immunomodulation might occur at the initiation of phototherapy with a return to control values on more prolonged UV exposure. Thus, in this study the responses of 15 patients with chronic plaque psoriasis undergoing broad-band UVB therapy, 10 narrow-band (311-313 nm) UVB therapy and 10 PUVA therapy were compared. In each case, samples were taken immediately before starting treatment and 1 week later. Broad-band UVB and PUVA therapy had no effect on NK activity, but a significant reduction was found in the group receiving narrow-band UVB. In vitro lymphoproliferative responses to mitogens and to herpes simplex virus antigens did not alter with therapy, except there was a significant increase in mitogen responses (at optimal mitogen concentrations only) in the narrow-band UVB group. Generally no alterations in overall percentages of circulating mononuclear cells were found in any group. Samples were taken from the epidermis of the forearm and back of the patients receiving narrow-band UVB for the quantification of urocanic acid (UCA) isomers. The total UCA concentration remained unchanged after 1 week of therapy, while the percentage of cis-UCA increased significantly at both sites in the majority of patients. However, this rise did not correlate with the decrease in NK cell activity and the two parameters may not be related causally.
Trans-urocanic acid (UCA) is found in the upper layer of the skin and UV irradiation induces its photoisomerization to cis-UCA. Cis-UCA mimics some of the immunosuppressive properties of UV exposure. The wavelength dependence for in vitro photoisomerization of trans-UCA (15 microM) over the spectral range 250 nm-340 nm (10 nm intervals) was determined. The action spectrum revealed that maximal cis-UCA production occurred at 280 nm, which is red-shifted by 10-12 nm from its absorption peak at 268 nm and differs markedly from the reported action spectra for cis-UCA production in mouse skin in vivo, which peaks at 300-310 nm. The reasons for the red shift between the in vitro and in vivo action spectra are not clear. There is limited evidence suggesting that the UV absorption maximum of trans-UCA red shifts from 268 nm in vitro to 310 nm on interaction with stratum corneum proteins in vivo. This phenomenon was investigated by applying trans-UCA (2.5 mg/cm2) in an oil emulsion to isolated human stratum corneum. After incubation at 37 degrees C for 1 h, the absorption spectra of stratum corneum with UCA and with oil only were compared using a Xe arc source and a spectroradiometer. A moderate red shift in trans-UCA absorption from approximately 268 nm to 280 nm was observed. In summary, we suggest that the 10-12 nm red shift between the UCA absorption spectrum peak and the action spectrum peak in vitro may be accounted for by the wavelength dependence of quantum yields reported over the 254-313 nm range. The red shift between the in vitro and in vivo photoisomerization action spectra may result from the 10 to 12 nm red shift in the absorption of UCA in association with stratum corneum proteins, combined with increasing quantum yields over the 254-313 nm range.
The kinetics of skin cancer induction by UV radiation has been extensively studied in hairless mice and described by Weibull statistics in which the time till 63% of the mice bear tumors is a primary parameter. However, the kinetics of the associated immunosuppression remained to be determined. To this end, we implanted a syngeneic UV-induced skin carcinoma cell line (T51/6.53) in the ventral skin of HRA/SKH hairless mice after various periods of daily dorsal UV exposure, either 150 or 75 mJ/cm2 per day UV from F40 sunlamps (regimens that when continued yield 63% of the mice with 1 mm tumors in 11.5 or 16.2 weeks, respectively). Both exposure regimens achieved a 100% acceptance (after 7 and 16 weeks, respectively). The implants failed to grow in all unirradiated control mice, but the percentage of mice in which the implants grew increased with the UV treatment time and dose. The estimated times to 63% implant acceptance were 4.3 +/- 0.8 and 8.2 +/- 0.8 weeks for the high and low daily doses, respectively. As reported earlier for shaved haired mice, there appears to be a straight reciprocity between daily UV dose and the time to tumor acceptance, i.e. the latter fully depends on the cumulative UV dose, whereas the tumor induction does not. The latter probably also depends on a pure elapse of time, i.e. UV-independent processes. A further analysis of the Weibull description indicates that immunosuppression toward the tumor requires fewer UV-driven steps that tumor induction.
Exposure to ultraviolet B (UVB) radiation results in the suppression of many cell-mediated immune responses, and recent studies mice and murine cells in vitro suggest a shift from a T-helper 1 (Th1) to a Th2 type of response on irradiation. Active psoriasis is considered to be a Th1-type disorder, chiefly on the basis of the cytokines produced by inflammatory cells in psoriatic lesions. We investigated the effect of phototherapy in patients with psoriasis on the cytokine profile of mitogen-stimulated mononuclear cells from peripheral blood and the concentration of IgG subclasses and IgE in the plasma. Eight patients were irradiated with a broad-band UV source (Sylvania UV6; 280-400 nm) three times a week and another eight with a narrow-band UVB source (Philips TL-01; 311-313 nm). Peripheral blood was collected before therapy started and after 1-4 weeks of therapy. Peripheral blood mononuclear cells were stimulated in vitro with phytohemagglutinin; proliferation was measured by incorporation of tritiated thymidine and culture supernatants assayed for interleukin (IL)-2, -4 and -10 and gamma-interferon (IFN) by enzyme-linked immunosorbent assays. Lymphoproliferation was not consistently affected by 4 weeks of UV6 therapy, and there was also no consistent change in the production of IL-2, IL-10 or gamma-IFN. In contrast, 4 weeks of TL-01 therapy significantly suppressed lymphoproliferative responses. In addition the production of IL-2, IL-10 and gamma-IFN was lowered after 1 week of TL-01 therapy, and this was even more apparent after the treatment had been extended to 4 weeks. IL-4 concentrations were below detectable levels in all the samples throughout the study. The amounts of IgG1, -2, -3 and -4 and IgE in the plasma of the patients did not vary with either of the two phototherapies. Thus, although no evidence was obtained to indicate that UV6 exposures affected T-helper subsets in psoriasis, TL-01 inhibited the activity of both Th1 and Th2 subsets while not altering plasma antibody concentrations.
The elTeci tfl: UVB irradJatkm. +'i,~ urocanic {Icid and ttlniotlr necrosis fachli .-f,~ 01/ delayed hypersensitivity to her pes shnplex virn'~. Pholod0rnlalo
- J W M Gilmour
J.W. Gilmour. M. Norval. The elTeci tfl: UVB irradJatkm. +'i,~ urocanic {Icid and ttlniotlr necrosis fachli.-f,~ 01/ delayed hypersensitivity to her pes shnplex virn'~. Pholod0rnlalo[. Pll(~l{ihnllltnlol. Pholollled. 9 (1993) 250-254.
Iournat o[ Photocl;cmi.slC~ and t'hotohiologv B: Biolok, y 42
- I Gars
I. Gars.~en el al. /,Iournat o[ Photocl;cmi.slC~ and t'hotohiologv B: Biolok, y 42 ( 19981 Ig)7 179
In\esii-gating tile red-shi[t between ill vivo and in vitro urocanic acid pho toisomerisation action spectra, Photo)chem. Photobiol
- A K Jones
- J Burton
- M Crosby
- N K Norval
- M Gibhs
- Guckian
- Joncs J Cd
- J Cooper
- R S Vestey
Jones, A.K. Burton. J. Crosby. M. Norval, N.K. Gibhs. In\esii-gating tile red-shi[t between ill vivo and in vitro urocanic acid pho toisomerisation action spectra, Photo)chem. Photobiol. (~ (1996) 302-305. [61 M. Guckian, CD, Joncs. J. Cooper, J.P Vestey, R.S, |)awe. N.K.
A:,konase, An earl) COlllpont'nl of dehl.ved hypersensitivit,> nicdiatod h\ T cells and illaM c011s
- H I R Vall
- P Meade
- v
H. Vall I,overen. R. Meade. P.\V. A:,konase, An earl) COlllpont'nl of dehl.ved hypersensitivit,> nicdiatod h\ T cells and illaM c011s. J. Exp. Med. 157 (1983) t6(i4-1hl7.
Pyrimidine dirner~ in DNA initiate s),siemic iminunosuppressiml in UV irradialed inicc
- M L Kripke
- P A L G Cox
- D B Ahls
- Yarosh
M.L. Kripke, P.A. Cox. L.G. Ahls. D.B. Yarosh. Pyrimidine dirner~ in DNA initiate s),siemic iminunosuppressiml in UV irradialed inicc. Prec. Natl. Acud. Sci. t]S.A, 89 ( 1992i 7516-7520.
omparative p~ltenc} ill different IIV sources m reducing the densily kind antigen presenling cupacJty ill inurine Langerhans cells Tile effects ellow dosc UVB radiath)n on l,angerhan, cells, sunburn cells, urocanic acid isomers, contact hypersensili\il} and scrtnn immunogh)bulins in mice
- A V1-Ghorr
- F Pierik
- M Norval
- A
- M Ei-Ghorr
- M Norval
- J C Crosby
A. V1-Ghorr, F. Pierik, M. Norval. ('omparative p~ltenc} ill different IIV sources m reducing the densily kind antigen presenling cupacJty ill inurine Langerhans cells. Photochem. Pholobiol. 60 f 1994) 256 261, A. EI-Ghorr. M. Norval, M,B. l,appin, J.C. Crosby. Tile effects ellow dosc UVB radiath)n on l,angerhan,, cells, sunburn cells, urocanic acid isomers, contact hypersensili\il} and scrtnn immunogh)bulins in mice. Photochcrn. Photobiol. 62 ( 1995i 326 332. W. Goclisch. Effects ill ultra\ icier Ir'l radiation on the resistance Io inlectious diseases. Ph.l). Thesis. 17niversh) of Utrocht I I '-)95 ).
Van 1,overen, Efl~:cls of ultraviolet-B exposure on the resistance to Listerm mm~oevto,~,e~e.~ in the rat, Photochem. Pho tohiol
- F R Gruijl
F.R de Gruijl, H. Van 1,overen, Efl~:cls of ultraviolet-B exposure on the resistance to Listerm mm~oevto,~,e~e.~ in the rat, Photochem. Pho tohiol. 63 { 1996) 672-670.
Exposure to low dose ultra~ hflet B light suppresses dehiyed I',pc h~ persensitivity it} herpes simplex \irus in mice
- In
- S Dornlatol
- M Howie
- J Nnrval
- Mahlgay
In,,e>i. DornlatOl. 1(12 ( 1994} 923 <)27. S. Howie, M. Nnrval, J. Mahlgay, Exposure to low dose ultra~ hflet B light suppresses dehiyed I',pc h~ persensitivity it} herpes simplex \irus in mice, ]. Invest. I)ermal~l. 8¢' ~ (1986) 125-128.
UV radiation and mouse models of herpes simple× virus infection, Photochem. Photobiol. 64 c 1096l 242 245 The effect of UV-B irradiation on second-ary epidermal infection of mice with herpes simplex virus type 1
- M Norval
M. Norval, A.A. F,1-Ghorr. UV radiation and mouse models of herpes simple× virus infection, Photochem. Photobiol. 64 c 1096l 242 245. ] 36 J A.A. E1-Ghorr, M. Norval, The effect of UV-B irradiation on second-ary epidermal infection of mice with herpes simplex virus type 1. J Gcn. Virol. 77 (1996) 485 491. ]37].
UV B induced suppression of the early initiating phase and the late effector phase of contact hypersensitivity to pieryl chloride is regulated by different mechanisms
- Sontag