No adaptation to UV-induced immunosuppression and DNA damage following exposure of mice to chronic UV-exposure

It is well known that ultraviolet (UV) radiation induces erythema, immunosuppression and carcinogenesis. We hypothesized that chronic exposure to solar UV radiation induces adaptation that eventually prevents the suppression of acquired immunity. We studied adaptation for UV-induced immunosuppression after chronic exposure of mice to a suberythemal dose of solar simulated radiation (SSR) with Cleo Natural lamps, and subsequent exposure to an immunosuppressive dose of solar or UVB radiation (TL12). After UV dosing, the mice were sensitized and challenged with either diphenylcyclopropenone (DPCP) or picryl chloride (PCl). To assess the adaptation induced by solar simulated radiation, we measured the proliferative response and cytokine production of skin-draining lymph node cells after immunization to DPCP, the contact hypersensitivity (CHS) response to PCl, and thymine-thymine (T-T) cyclobutane dimers in the skin of mice. After induction of immunosuppression by SSR or by TL12 lamps, the proliferative response of draining lymph node cells after challenge with DPCP, or the CHS after challenge with PCl, showed significant suppression of the immune response. Chronic irradiation from SSR preceding the immunosuppressive dose of UV failed to restore the suppressed immune response. Reduced lipopolysaccharide-triggered cytokine production (of IL-12p40, IFN-gamma, IL-6 and TNF-alpha) by draining lymph node cells of mice sensitized and challenged with DPCP indicated that no adaptation is induced. In addition, the mice were not protected from T-T dimer DNA damage after chronic solar irradiation. Our studies reveal no evidence that chronic exposure to low doses of SSR induces adaptation to UV-induced suppression of acquired immunity.     

Decrease in langerhans cells and increase in lymph node dendritic cells following chronic exposure of mice to suberythemal doses of solar simulated radiation

Exposure of certain strains of mice to ultraviolet radiation (UVR) causes suppression of some innate and adaptive immune responses. One such consequence of acute UVB exposure is a reduction in the number of Langerhans cells (LC) in the epidermis and an increase in dendritic cells (DC) in lymph nodes draining the irradiated skin sites. Exposure to chronic UVB irradiation also has effects on the immune system, but it is unknown what effects are caused by repeated doses of solar simulated radiation (SSR). Consequently, the main aims of the present study were to determine whether repeated exposure to low doses of SSR would lead to similar changes in these cell populations and whether chronic doses of SSR activate a protective photoadaptation mechanism. Groups of C3H/HeN mice were irradiated daily with 3.7 J/cm(2) SSR from Cleo Natural lamps for 2, 10, 20, 30 or 60 days. Further groups of mice received an additional dose of 7.4 J/cm(2) SSR on days 2, 10, 30 or 60 to test for photoadaptation. The numbers of LC in the epidermis and DC in the lymph nodes draining irradiated skin sites were counted 24 h after the final irradiation. With the exception of mice irradiated for only 2 days, LC were significantly reduced throughout the chronic irradiation protocol, and no recovery occurred. DC numbers were significantly increased in the draining lymph nodes of mice irradiated for 20 days and 60 days.     

UV index forecasts and measurements of health-effective radiation

While erythemal irradiance as a potentially damaging effect to the skin has been extensively studied and short-term forecasts have been issued to the public to reduce detrimental immediate and long-term effects such as sunburn and skin cancer by overexposure, beneficial effects to human health such as vitamin D(3) production by UV radiation and melatonin suppression by blue visible light have attained more and more attention, though both of them have not become part of forecasting yet. Using 4years of solar radiation data measured at the mid-latitude site Lindenberg (52°N), and forecast daily maximum UV index values, an overall good correspondence has been found. The data base of solar UV radiation and illuminance has also been used to analyze effects of clouds and aerosols on the effective irradiance. Optically thick clouds can strongly modify the ratios between erythemal and vitamin D(3) effective irradiance such that direct radiative transfer modeling of the latter in future UV forecasts should be preferably used. If parameterizations of vitamin D(3) effective irradiance from erythemal irradiance are used instead, the optical cloud depth would have to be taken into account to avoid an overestimation of vitamin D(3) with parameterizations neglecting cloud optical depth. Particular emphasis for the beneficial effects has been laid in our study on low exposure. Daily doses of solar irradiation for both vitamin D(3) and melatonin suppression do not reach minimum threshold doses even with clear sky and unobstructed horizon during the winter months.     

Kinetics of UV light-induced cyclobutane pyrimidine dimers in human skin in vivo: an immunohistochemical analysis of both epidermis and dermis

It is well known that UV exposure of human skin induces DNA damage, and the cumulative effect of such repeated damage is an important contributor to the development of skin cancer. Here, we demonstrate UV dose- and time-dependent induction of DNA damage in the form of cyclobutane pyrimidine dimers (CPD) in skin cells following a single exposure of human skin to UV radiation. CPD+ cells were identified by an immunohistochemical technique using monoclonal antibodies to thymine dimers. The percentage of CPD+ cells was UV dose-dependent, even a suberythemal (0.5 minimal erythemal dose [MED]) dose resulted in detectable level of cells that contained pyrimidine dimers. Forty-eight hours after irradiation the percent of total epidermal cells positive for CPD ranged from 19 +/- 8, 36 +/- 10, 57 +/- 12 and 80 +/- 10, and total percent dermal cells positive for CPD ranged from 1 +/- 1, 7 +/- 3, 16 +/- 3 and 20 +/- 5, respectively, following 0.5, 1.0, 2.0 and 4.0 MED. CPD were also observed in deeper reticular dermis, which suggest the penetrating ability of UV radiation into the skin. The change in CPD+ cells from 0.5 to 240 h post-UV exposure in both epidermal and dermal compartments of the skin was also quantitated. CPD+ cells were observed in skin biopsies at early time points after UV exposure which remained elevated for 48 h, then declined significantly by 3 days post-UV. A close examination of the skin at and after 3 days following UV exposure indicates the significant removal of DNA damaged cells from the epidermis. Ten days after UV exposure the levels of CPD+ cells in both epidermis and dermis were not significantly different from that in unirradiated skin.     

Occupational UV Exposure of Environmental Agents in Valencia,Spain

Excessive exposure to ultraviolet radiation (UVR) is considered the most important environmental risk factor in the development of melanoma and skin cancer. Outdoor workers are among those with the highest risk from exposure to solar UVR, as their daily activities constantly expose them to this radiation source. A study was carried out in Valencia, Spain, in summer 2012 and involved a group of 11 workers for a period of six 2‐day recordings. Sensitive spore‐film filter‐type personal dosimeters (VioSpor) were used to measure erythemal UVR received by environmental agents in the course of their daily work. Median 2‐day UV exposure was 6.2 standard erythema dose (SED), with 1 SED defined as effective 100 J m^?2 when weighted with the Commission Internationale de L′Eclairage's (CIE) erythemal response function. These workers were found to receive a median of 8.3% total daily ambient ultraviolet erythemal radiation. Comparison with the occupational UV exposure limit showed that the subjects had received an erythemal UV dose in excess of occupational guidelines, indicating that protective measures against this risk are highly advisable.     

Noninvasive Assessment of UV-induced Skin Damage: Comparison of Optical Measurements to Histology and MMP Expression

Acute exposure to UV radiation (UVR) causes visible skin damage such as erythema and results in local and systemic immunosuppression while chronic exposure can result in photocarcinogenesis. These deleterious effects can be quantified by histology and by bioassays of key biological markers, including matrix metalloproteinases (MMPs), or tryptophan moieties. We now report our results in quantifying UV skin damage with noninvasive optical methods based on reflectance and fluorescence spectroscopy and compare these noninvasive measurements to histopathology and MMP-13 expression. A solar simulator with spectral output nearly identical to that of solar radiation was developed and used in our experiments. SKH1 hairless mice were exposed to solar-simulated UVR at a total dose of 21 MED delivered over 10 weeks. Changes in oxygenated and deoxygenated hemoglobin were measured by diffuse reflectance spectroscopy, and tryptophan changes were monitored via a fluorescence monitor. Our results show that there is an increase in erythema, skin fluorescence, sunburn cells and MMP-13 after a series of suberythemal doses of UV irradiation on a hairless mouse animal model. Increased skin fluorescence is observed with increasing UV exposure. The levels of MMP-13 increase as the cumulative UV dose increases but their increase does not correspond to noninvasively measured changes.     

Wavelength dependence of histological, physical, and visible changes in chronically UV-irradiated hairless mouse skin

Albino hairless mice (Skh: HR-1) exposed chronically to sub-erythemal doses of UV radiation display physical, visible and histological alterations. Using narrow bandwidth radiation covering the UV radiation spectrum from 280-380 nm, the wavelength dependence of these alterations was determined. The wavelength dependence spectra indicate that for all but one parameter measured (skin sagging), UV-B radiation is considerably more efficient than UV-A radiation in producing changes in the skin. However, in natural sunlight there is considerably more UV-A than UV-B radiation, providing the potential for UV-A to have a larger contribution to skin damage than UV-B. This argues in favor of using broad spectrum photoprotective agents to shield the skin adequately from UV-induced aging. The spectra were also used to develop potential associations among events by determining which events occur at similar wavelengths. There seems to be a correspondence between mouse visible skin wrinking (UV-B event) and two histological events: increase in glycosaminoglycans and alteration in collagen. There was no obvious correspondence among UV-A-induced events.     

FAILURE OF UVR DOSE RECIPROCITY FOR SKIN TUMORIGENESIS IN HAIRLESS MICE TREATED WITH 8-METHOXYPSORALEN

Abstract— 8-Methoxypsoralen (8-MOP) phototumorigenesis was studied in hairless albino mice irradiated with solar simulated radiation (SSR). Animals were exposed to three different daily doses of SSR after application of an oily vehicle with or without 8-MOP. Tumor production was dependent on daily SSR dose irrespective of topical treatment. The phototumorigenic potency of SSR was increased by the vehicle and to a much greater extent by inclusion of 8-MOP. Irrespective of topical treatment, a failure in dose reciprocity for tumorigenesis was demonstrated; in terms of cumulative SSR dose, the lower daily doses were more tumorigenic than the higher doses. This reciprocity failure in 8-MOP photosensitized mice is similar to that previously observed for UV-B phototumorigenesis. The relevance of these findings to therapeutic use of psoralens is discussed.     

Anatomical distribution of solar ultraviolet exposures among cyclists

Exposure to solar ultraviolet (UV) radiation is the major environmental factor implicated in the development of melanoma and other skin cancers, as well as eye damage and skin photoaging. Outdoor recreational activities such as cycling are increasingly pursued for health benefits, however little information is available regarding potential adverse effects of excessive sun exposure in this setting, nor about the anatomical distribution of solar dose. Polysulphone badges (UV dosimeters) were attached to the head, backs of hands and ankles of 22 cyclists during a seven-day charity bicycle ride in Queensland, Australia. Average daily exposures exceeded one minimal erythemal dose (MED) at all body sites except the ankle. Significant differences in UV dose among the various body sites were noted, with highest exposures recorded on the top of the head. Mean doses received at the ankle (0.94 MED), back of the hand (1.28 MED) and side of the head (1.14 MED) were 51%, 71% and 63% of those received at the top of the head (1.80 MED), respectively. These data indicate that cycling exposes adherents to substantial doses of UV radiation. Moreover, our observations suggest that even vertically-oriented, potentially shaded sites such as the lower leg typically receive doses of solar radiation no less than half of maximally exposed sites.     

UV index experimental values during the years 2000 and 2001 from the Spanish broadband UV-B radiometric network

An analysis is made of experimental ultraviolet erythemal solar radiation data measured during the years 2000 and 2001 by the Spanish UV-B radiation evaluation and prediction network. This network consists of 16 Robertson-Berger type pyranometers for evaluating solar erythemal radiation and five Brewer spectroradiometers for evaluating the stratospheric ozone. On the basis of these data the Ultraviolet Index (UVI) was evaluated for the measuring stations that are located either in coastal regions or in the more densely populated regions inland on the Iberian Peninsula. It has been checked that in most cases the maximum irradiance values corresponded to solar noon, although there were exceptions that could be explained by cloudiness. The maximum experimental values of the UVI were around 9 during the summer, though frequently passing this value at the inland measurement stations. The annual accumulated dose of irradiation on a horizontal plane has also been studied, as well as the evolution through the year in units of energy, standard erythemal doses and minimum erythemal doses, according to different phototypes.     

OBSERVED AND PREDICTED MINIMAL ERYTHEMA DOSES: A COMPARATIVE STUDY

Abstract This study compared how well minimal erythema doses predicted using the reference action spectrum for UV erythema proposed by the International Commission on Illumination (CIE) in 1987 agreed with those observed in phototesting a large number of subjects with normal responses to sunlight to six different wavelengths of UV radiation (UVR) between 300 and 400 nm. It was found that, within the limits of experimental error, the hypothesis that the CIE reference action spectrum is a valid predictor of the erythemal effectiveness of different wavelengths of UVR could not be dismissed. There is no strong reason, therefore, why the CIE action spectrum should not continue to be used as a reference to compare the erythemal effectivenesses of different broadband sources. However, close examination of the residuals from the regression analysis suggested that the erythemal sensitivity of skin at longer UV wavelengths (>350 nm) in the population studied here is greater than predicted from the CIE reference action spectrum.     

An estimation of biological hazards due to solar radiation

A spectrum evaluator based on four different dosimeter materials has been employed to estimate the spectral irradiances of solar radiation for exposed humans. The result is used to calculate the biologically effective irradiance using the erythemal action spectrum and a fish melanoma action spectrum. Measurements are made in winter at a sub-tropical site on the chest and shoulder of subjects during normal daily activities. Up to 95% of the total UV exposure received is in the UV-A waveband (320-400 nm). The UV-A waveband is found to contribute approximately 14% of the erythemal UV and 93% of the biologically effective UV for fish melanoma. Extrapolation to humans suggests that exposure to the UV-A band will contribute to photodamage in human skin during exposure to solar radiation.     

Analysis of Two Kinds of Tree as Physical Barriers Against Erythemal UVB Radiation Received

Differences between global radiation UVER (erythemal ultraviolet solar radiation) received under full sun and diffuse radiation received under the shadow of two types of tree are analyzed to check the importance of these components on human exposure to UV radiation. Blue Line spores dosimeters of VioSpor were used for measurement of erythemal dose of UV radiation (able to produce erythema in human skin.) The response profile of these devices is extremely similar to human skin, thus they are suitable to determine and predict the interactions between UV erythema and human skin. Measurements were obtained in relatively clear days from February to December 2009 between 9:30 and 15:30 h. Three dosimeters were placed on a horizontal surface: one in full sun and the other two under the shadow of each tree. Values of UVER in both cases, in full sun and under the shadow of pine and Sauce, were obtained. In addition, the comparison was made between values of dose received in each case and the exposure limits recommended by the International Commission on Non‐Ionizing Radiation Protection (ICNIRP). Finally, average daily irradiance received under the shadow of each tree in comparison with those received in full sun, was also analyzed using two PMA2100 radiometers situated on a horizontal surface.     

The European Light Dosimeter Network: four years of measurements

The European Light Dosimeter Network (ELDONET) has now been functional for more than four years. The network is based on dosimeters which measure radiation in three biologically relevant wavelength bands (UV-B, 280-315 nm; UV-A, 315-400 nm; and Photosynthetic Active Radiation, PAR, 400-700 nm). The ELDONET network is currently based on 33 stations with 40 instruments. The distribution of the instruments all over Europe allows measurement of the latitudinal and longitudinal light climate distribution. In addition, several instruments are active in South America, New Zealand, India, Africa and Japan. With some exceptions, the measured yearly doses depend on the latitude. While the maximal daily doses are almost comparable from station to station, seasonal changes and the different maximal solar zenith angles account for the differences in total yearly doses. Ratioing between UV-B and PAR allows the detection of subtle changes in the local light climate, due, for example, to mini-ozone holes encountered in northern Europe during spring. Comparison of satellite ozone data with terrestrial ELDONET measurements revealed an overall weak correlation between these data sets. However, local weather conditions, solar zenith angle and latitude as well as reflectivity (i.e. clouds and aerosol; satellite data) show a much stronger correlation to the doses received. The close relationship between the spectral sensitivity of the UV-B sensor used in the ELDONET dosimeter and the CIE erythemal action spectrum allows determination of the erythemal dose on the basis of the dosimeter readings.     

The effects of grape seeds polyphenols on SKH-1 mice skin irradiated with multiple doses of UV-B

The study investigated the protective activity of red grape seeds (Vitis vinifera L, Burgund Mare variety) (BM) extracts in vivo on multiple doses of ultraviolet radiation (UV)-B-induced deleterious effects in SKH-1 mice skin. Eighty 8-weeks-old female SKH-1 mice were divided into 8 groups: control, vehicle, UV-B irradiated, vehicle+UV-B irradiated, BM 2.5mg polyphenols (PF)/cm(2)+UV-B irradiated, BM 4 mg PF/cm(2)+UV-B irradiated, UV-B+BM 2.5mg PF/cm(2), UV-B+BM 4 mg PF/cm(2). The extract was applied topically before or after each UV-B exposure (240 mJ/cm(2)), for 10 days consecutively. The antioxidant activity of BM extract is higher than gallic acid (k(BM)=0.017, k(gallic acid)=0.013). Multiple doses of UV-B generated the formation of cyclobutane pyrimidine dimers (CPDs) and sunburn cells, increased glutathione peroxidase (GPx) and catalase (CAT) activities respectively glutathione (GSH) and IL-1β levels in skin. In group treated with 2.5mg PF/cm(2) before UV-B irradiation BM extract inhibited UV-B-induced sunburn cells, restored the superoxide dismutase (MnSOD) activity, increased insignificantly CAT and GPx activities and reduced IL-1β level. The BM 4.0 mg PF/cm(2) treatment decreased GSH level and reduced the percentage of CPDs positive cells in skin. Both doses of BM extract administered after UV-B irradiation increased the MnSOD and GPx activities and reduced the formation of sunburn cells in skin. Our results suggest that BM extract might be a potential chemo-preventive candidate in reducing the oxidative stress and apoptosis induced by multiple doses of UV-B in skin.     

UV-induced changes in pigment content and light penetration in the fruticose lichen Cladonia arbuscula ssp. mitis

The response of the lichen, Cladonia arbuscula (Wallr.) Flot. ssp. mitis (Sandst.) Ruoss to enhanced UV-B (280-315 nm) radiation was investigated with respect to: (a) changes in phenolic content; (b) differential pigment accumulation under visible and UV radiation with increasing distance from thallus apices; and (c) the internal distribution of UV-B radiation within the thallus measured with quartz optical fibres. In a short-term experiment, lichens were exposed for 7 days in a growth chamber to visible light with or without additional UV-B radiation. For a longer term experiment, lichens were grown outdoors under both natural UV radiation, and supplemental UV-A (315-400 nm)+UV-B provided by lamps. Controls were placed under filters that removed the radiation below 290 nm from the natural sunlight. The concentration of total phenolic compounds was measured spectrophotometrically at the termination of the experiments, in different parts of the lichen podetia. UV-exposed lichens showed increased accumulation of phenolics compared to those not grown under UV. At the termination of the long-term experiment, fibre optic measurements of the penetration of radiation into lichen thallus reflected the influence of growth under UV radiation, whereby UV was more strongly attenuated as compared to that in lichens not exposed to enhanced levels of UV-B radiation. Results indicated that in Cladonia, UV-B radiation induces the accumulation of phenolic compounds that may have a protective role. In addition, the morphological distribution of phenolic compounds was different under visible and supplemental UV-B radiation. Internal radiation measurements served to visualise the attenuation of radiation with thallus depth for different wavelengths in the UV-B waveband.     

Isomerization of urocanic acid after ultraviolet radiation is influenced by skin pigmentation

Exposure to ultraviolet (UV) radiation may induce erythema, DNA damage and suppression of immune responses. Melanin pigmentation offers protection against the first two of these effects, but immunosuppression seems to occur irrespective of the subject's pigmentation. Cis-urocanic acid (cis-UCA), produced by isomerization of trans-UCA in the stratum corneum on UV exposure, initiates some of the immunomodulatory effects of UV radiation. In the present study the relationship between skin pigmentation and UCA isomerization has been examined in 28 healthy individuals of skin types I-IV. Pigmentation is measured in five areas of not recently exposed back skin before irradiation with 0, 0.45, 0.9, 1.8 and 3.6 standard erythema dose (SED) of filtered broadband UV-B (1 SED = 10 mJ cm-2 at 298 nm). The concentration of UCA isomers is measured immediately after the irradiation. With 3.6 SED, the relative production of cis-UCA is close to the maximum obtainable, irrespective of skin type. A significant negative correlation is found between pigmentation and relative production of cis-UCA at 0.45 and 1.8 SED, and between pigmentation and absolute production of cis-UCA at 0.45 SED. At doses of 0.45 and 0.9 SED the relative and absolute production of cis-UCA are higher in the group with skin types I and II when compared with the group with skin types III and IV. The higher isomerization in the lightly pigmented subjects than in the more pigmented ones may indicate that people with fair skin are at a relatively higher risk of immunosuppression when exposed to low doses of UV radiation.     

Salt water bathing prior to UVB irradiation leads to a decrease of the minimal erythema dose and an increased erythema index without affecting skin pigmentation

The combination of salt water baths and solar radiation is known as an effective treatment for patients with psoriasis and atopic dermatitis. To determine whether increased susceptibility to UVB radiation may contribute to this therapeutic effect we have studied the effect of bathing the skin in salt water prior to UVB irradiation. Twelve subjects were phototested on the volar aspects of their forearms with increasing doses of UVB radiation. One forearm was exposed to 5% salt water prior to irradiation. The minimal erythema dose (MED) was determined and the erythema index and skin pigmentation were assessed by photometric measurement. The combination of salt water bath and irradiation yielded a significant decrease of the MED when compared to UVB alone (median 90 mJ/cm2 vs 130 mJ/cm2, P < 0.01). Analysis of variance showed a significant influence of salt water bath on erythema (P < 0.05) but not on skin pigmentation. Within the MED test area the erythema index of the salt water exposed forearms was elevated significantly (P < 0.05) while skin pigmentation was not affected. Thus, bathing the skin in salt water leads to a decreased threshold level for the elicitation of UVB-induced erythema and a selective increase of the erythemal response. This sensitization to the effects of shortwave UVB radiation may increase immunosuppressive effects of UVB radiation and may lead to an increased efficacy of UVB phototherapy. However, there is also an increased sunburn risk when salt water baths are followed by exposure to UV radiation.     

Inflammatory doses of UV may not be necessary for skin carcinogenesis

The UV wavelengths in sunlight are the main cause of skin cancer in humans. Sunlight causes gene mutations, immunosuppression and, at higher doses, inflammation. While it is clear that immunosuppression and gene mutations are essential biologic events via which UV causes skin cancer, the requirement for UV-induced inflammation is less certain. Both the UVB (290-320 nm) and UVA (320-400 nm) wavebands within sunlight can cause skin cancer, gene mutations and immunosuppression. However, UVB, but not UVA, at realistic doses can cause inflammation, and UVB induces skin cancer, immunosuppression and gene mutations at doses much lower than those required to cause inflammation. Inflammation enhances skin carcinogenesis, but may not be UV induced, and inflammatory mediators at doses too low to cause inflammation may be required. UV-induced mutations can cause epidermal cells to make proinflammatory factors or to induce them in the surrounding stroma, creating an oxidizing environment in which additional oncogenic mutations are likely to take place, even in the absence of UV. Our hypothesis is therefore that subinflammatory doses of both UVA and UVB cause benign skin tumors. One of the effects of sunlight-induced mutations may be the production of inflammatory mediators that enhance carcinogenesis.     

Influence of eicosapentaenoic acid, an omega-3 fatty acid, on ultraviolet-B generation of prostaglandin-E2 and proinflammatory cytokines interleukin-1 beta, tumor necrosis factor-alpha, interleukin-6 and interleukin-8 in human skin in vivo

Dietary omega-3 polyunsaturated fatty acids (omega-3 PUFA) reduce sunburn, an acute inflammatory response, in humans. We assessed whether this may be mediated by reduced ultraviolet-B (UV-B) induction of proinflammatory mediators tumor necrosis factor-alpha (TNF-alpha), interleukin (IL)-1 beta, IL-6, IL-8 and prostaglandin (PG)E(2) in healthy skin. In a double-blind, randomized study, 28 humans received 4 g daily of 95% ethyl esters of eicosapentaenoic acid (EPA) or oleic acid (OA) orally for 3 months. Skin biopsies and suction blister fluid were taken from unexposed and UV-B-exposed skin and examined for mediator expression immunohistochemically and quantitatively by immunoassay; plasma levels were also assayed. The subjects taking EPA, but not OA, showed a significant rise in their minimal erythemal dose (MED) (data reported elsewhere). Before supplementation, irradiation with 3x MED UV-B increased blister fluid TNF-alpha, IL-6, IL-8 and PGE(2) at 16 h (all P < 0.001). No significant change occurred in baseline or UV-B-induced skin levels of cytokines after either supplement, whereas UV-B induction of PGE(2) was abolished after EPA but not OA. Immunohistochemical expression of the cytokines at baseline and after UV-B was unaltered by EPA and OA; circulating cytokine and PGE(2) levels were also unchanged. Hence, in healthy skin in vivo, there was no evidence that reduction of the sunburn response by EPA is mediated by the proinflammatory cytokines examined; abrogation of UV-B-generated PGE(2) may play a role.