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.     

Changes in matrix gene and protein expressions after single or repeated exposure to one minimal erythemal dose of solar-simulated radiation in human skin in vivo

Damage to the skin extracellular matrix (ECM) is the hallmark of long-term exposure to solar UV radiation. The aim of our study was to investigate the changes induced in unexposed human skin in vivo after single or repeated (five times a week for 6 weeks) exposure to 1 minimal erythemal dose (MED) of UV solar-simulated radiation. Morphological and biochemical analyses were used to evaluate the structural ECM components and the balance between the degrading enzymes and their physiologic inhibitors. A three-fold increase in matrix metalloproteinase 2 messenger RNA (mRNA) (P < 0.02, unexposed versus exposed) was observed after both single and repeated exposures. Fibrillin 1 mRNA level was increased by chronic exposure (P < 0.02) and unaltered by a single MED. On the contrary, a single MED significantly enhanced mRNA levels of interleukin-1alpha (IL-1alpha), IL-1beta (P < 0.02) and plasminogen activator inhibitor-1 (P < 0.05). Immunohistochemistry demonstrated a significant decrease in Type-I procollagen localized just below the dermal-epidermal junction in both types of exposed sites. At the same location, the immunodetected tenascin was significantly enhanced, whereas a slight increase in Type-III procollagen deposits was also observed in chronically exposed areas. Although we were unable to observe any change in elastic fibers in chronically exposed buttock skin, a significant increase in lysozyme and alpha-1 antitrypsin deposits on these fibers was observed. These results demonstrate the existence of a differential regulation, after chronic exposure compared with an acute one, of some ECM components and inflammatory mediators.     

Objective measurement of minimal erythema and melanogenic doses using natural and solar-simulated light

Very little information exists on the amount of natural and artificial UV light required to cause sunburn and tanning in individuals with very pale skin who are at the greatest risk of developing skin cancer. We have investigated minimal erythema dose (MED) and minimal melanogenic dose (MMD) in a group of 31 volunteers with Fitzpatrick skin types I and II using an Oriel 1000 W xenon arc solar simulator and natural sunlight in Sydney, Australia. We measured the erythemal and melanogenic responses using conventional visual scoring, a chromameter and an erythema meter. We found that the average MED measured visually using the artificial UV source was 68.7 +/- 3.3 mJ/cm2 (3.4 +/- 0.2 standard erythema doses [SED]), which was significantly different from the MED of sunlight, which was 93.6 +/- 5.6 mJ/cm2 (P < 0.001) (11.7 +/- 0.7 SED). We also found significant correlations between the solar-simulated MED values, the melanin index (erythema meter) and the L* function (chromameter). The average MMD (obtained in 16 volunteers only) using solar-simulated light was 85.6 +/- 4.9 mJ/cm2, which was significantly less than that measured with natural sunlight (118.3 +/- 8.6 mJ/cm2; P < 0.05). We mathematically modeled the data for both the chromameter and the erythema meter to see if we were able to obtain a more objective measure of MED and differentiation between skin types. Using this model, we were able to detect erythemal responses using the erythema index function of the erythema meter and the a* function of the chromameter at lower UV doses than either the standard visual or COLIPA methods.     

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.     

p53 induction in normal human skin in vitro following exposure to solar simulated UV and UV-B irradiation.

Exposure of normal human breast skin ex vivo to physiological levels of UV-B and solar simulated UV results in a UV dose- and time-dependent increase in epidermal p53, as determined by PAGE analysis. Peak p53 levels are detected 12 to 24 h post irradiation with UV-B (470-1410 mJ cm-2) and solar simulated UV (5-12 minimal erythema dose (MED) equivalents). Irradiation with an FS20 UV-B lamp, contaminated with UV-A and UV-C (74-1111 mJ cm-2), also induces peak levels after 12 h incubation at 37 degrees C but these levels persist to 36 h post UV irradiation. In all cases p53 levels start to return to normal by 48 h culture. A significant positive correlation is demonstrated between UV-B dose (47-1645 mJ cm-2) and p53 level (p < 0.01, R > 0.977) in explants cultured for 24 h at 37 degrees C post irradiation. The FS20 induces a 'UV-B' dose-dependent increase in p53 to a maximum from 370 to 1111 mJ cm-2. Similarly, solar simulated UV induces a plateau of peak p53 induction between 5 and 15 MED equivalents. Immunohistochemical analysis using microwave retrieval on 5 microns sections shows the same pattern of p53 staining with UV-B and solar UV insult, but proves unreliable as a method of quantification. These results suggest that the skin explant model may be a useful tool in the evaluation of UV-induced epidermal cell damage, providing a valuable alternative to in vivo studies.     

Matrix metalloproteinase-1 production observed after solar-simulated radiation exposure is assumed by dermal fibroblasts but involves a paracrine activation through epidermal keratinocytes

Chronic exposure of human skin to solar UV radiation leads to serious dermal damages, a hallmark of photoaging. In vivo, acute UV radiation has been shown previously to induce various matrix-degrading proteases. Among them, matrix metalloproteinase-1 (MMP-1) has been suggested to be involved in skin photodamage. The purpose of this study was to investigate the effects of solar-simulated radiation (SSR) on MMP-1 production in normal human skin cells. SSR exposure of human skin reconstructed in vitro comprising both a differentiated epidermis and a fibroblast-populated dermal equivalent led to an increase in MMP-1 production, which was abolished when epidermis was removed immediately after SSR exposure. In addition, SSR exposure of differentiated keratinocytes grown on an acellular collagen gel did not induce MMP-1 production. Experiments on cell cultures grown on plastic confirmed that keratinocytes failed, in contrast with fibroblasts, to produce MMP-1 in response to SSR exposure. However, when conditioned medium from SSR-exposed keratinocytes was added to human fibroblasts in culture, MMP-1 production was induced. Altogether, these data show that MMP-1 production observed after SSR exposure involved the release of soluble epidermal factors, which could modulate its production by dermal fibroblasts.     

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.     

Measurement of in vivo sunscreen immune protection factors in humans

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

Reference limits for erythema-effective UV doses

Diagnostic phototesting, including the determination of the minimal erythema dose (MED), is a useful procedure to detect abnormal sensitivity to UV radiation. We aimed to estimate the reference limits (RLs) of the MED in a reasonably large reference sample of white individuals. Skin phototypes and MED values for broadband UVB and for UVA were determined in 461 white subjects. When appropriate, the 95% reference intervals, including the 0.025 fractile and 0.975 fractile, were computed for the MED-UVB reference values (by means of parametric methods) and the MED-UVA reference values (by means of nonparametric methods). MED data were also converted to standard erythema doses (SEDs). As described elsewhere we observed a considerable overlap of MED values for all skin phototypes and confirmed that age and sex do not substantially influence the MED. The lower RLs observed for MED-UVB were 33 mJ cm(-2) (0.5 SEDs) and for MED-UVA 12.6 mJ cm(-2) (1.2 SEDs). The MED and SED findings from this investigation may serve as reference data for white individuals and give support to the clinician in differentiating between normal and pathologically abnormal photosensitivity. Although the MED data given here are limited to the phototest device used in the present study, the SED results establish comparability between our data and phototest results obtained from laboratories using different UV sources.     

UV-induced unscheduled DNA synthesis in human skin: dose response, correlation with erythema, time course and split dose exposure in vivo

Unscheduled DNA synthesis (UDS) has been shown to be saturated above a threshold dose of UV-C in human fibroblasts in vitro. We have investigated by autoradiography whether a similar saturation occurs in human skin in vivo with UV-B and whether this phenomenon correlates with the erythemal response. In addition, we determined the time course of UDS at 24 h after exposure and the effect of dual exposures separated by 24 h. The dose-response curve was established by exposure to 1/16, 1/8, 1/4, 1/2, 1, 2, 3, 4 and 6 MEDs UV-B. For the time-course study, areas exposed to 1/2 and 2 MEDs were biopsied after 1, 3, 6, 12 and 24 h. Autoradiography was performed in vitro. The dose-response curve showed a significant increase in UDS from 1/16 to 1 minimal erythema dose (MED), whereas no significant difference was observed between 1 MED and the higher UV-B doses tested. The 24 h time sequence revealed a gradual decrease in UDS activity. The 1/2 MED curve declined more rapidly and reached the zero-level between 12 h and 24 h, whereas about 50% of the initial UDS value was still retained 24 h after 2 MEDs. The dual-dose study revealed that a second hit of fractions of the MED resulted in lower levels of UDS than induced by these fractions alone in previously untreated areas. UDS increases with the erythemal dose between 1/16 and 1 MED. It reaches a plateau after 1 MED and cannot be increased by doses up to 6 MEDs, suggesting a saturation of excision repair in vivo. Time course studies support such a saturation phenomenon. The failure to increase significantly UDS by a second irradiation 24 h after the first exposure needs further clarification. Since persistence of DNA lesions may lead to an accumulation after repeated exposures, additional mechanisms other than excision repair may protect human skin by error-free removal of possibly mutagenic sites. Photoreactivation may be important in this respect.     

EFFECT OF CHRONIC UV EXPOSURE ON EPIDERMAL FORWARD SCATTERING-ABSORPTION INSK–1 HAIRLESS MOUSE SKIN

Abstract— Clinical and histological precancerous responses to UV irradiation are complicated dynamic functions of total dose, dose fractionation, fluence rate, and spectral distribution. This may be due, in large part, to the ability of UV to decrease epidermal-stratum corneum transmission by stimulation of hyperplasia. This work provides quantitative measurement of dose- and wavelength-dependent optical changes inSK–1 hairless mouse epidermis-stratum corneum occurring under irradiation with “monochromatic” UV wavebands, at 280, 290, 300, 307, and 313 nm. Mice were irradiated 5 days per week with a filtered Xenon-Hg high-intensity grating monochromator, starting with 0.9 minimal erythemal dose (MED), followed by incremental increases in the radiation dose by 20% of the original dose every tenth irradiation day, for2–8 consecutive weeks. Subsequent irradiations (for longer experiments) were followed by 30% incremental increases after the 8th week every 10th irradiation day until cessation of radiation at the end of 14 weeks. Irradiated and control full-thickness epidermis/ stratum corneum were examined histologically and by forward-scattering absorption spectroscopy. Chronic irradiation of hairless mice resulted in significant hyperplasia which was optically manifested by a general increase in forward-scattering absorbance. At moderate local doses (7.2 MED), the absorbance increase per MED was approximately the same for all excitation wavelengths, whereas at large total doses (? 100 MED) the optical increase per delivered MED progressively decreased in the order 313> 307> 300? 290> 280 nm. The increase in skin thickening, expressed as observed increase in absorption at 320 nm, correlated well with histological and clinical data. We propose that optical changes induced by UV-induced thickening can account in large part, if not entirely, for dynamic changes in action spectra for (pre) cancerous processes under chronic irradiation conditions.     

Assessment of cutaneous photosensitivity of TOOKAD (WST09) in preclinical animal models and in patients

TOOKAD (WST09) is a new, long-wavelength palladium bacteriopheophorbide photosensitizer that targets tissue vasculature. The cutaneous phototoxicity of TOOKAD was assessed in normal rat and pig animal models and in patients in a Phase-I trial of TOOKAD-mediated photodynamic therapy (PDT) for recurrent prostate cancer. Controlled skin exposures were administered using solar-simulated light at various times after drug administration. Two different spectral ranges were used. In the first, the UV portion of the spectrum was removed (UV(-)) because UV irradiation in nondrugged control animals produced an erythema response at incident energy densities (J/cm(2)) lower than those required to induce a PDT response. In the second, the full solar spectrum (UV(+)) was used, and the potentiation by the photosensitizer of the UV-mediated minimum erythema dose was assessed. Results showed that the PDT skin response was negligible at clinical drug doses of 2 mg/kg for any period after administration at light doses of 128 J/cm(2) in the animal models. In patients, there was no observed UV(-) skin response at doses of up to 2 mg/kg, drug-light intervals of 1-3 h or greater and light exposures up to 128 J/cm(2). At higher drug doses in the rat and pig models, the duration of skin phototoxicity was found to be approximately 3 h and less than 1 h, respectively. Using the full spectrum of solar-simulated light, the presence of TOOKAD did not measurably enhance the UV(+)-induced erythema in the rats, pigs or patients.     

Neutrophil infiltration in normal human skin after exposure to different ultraviolet radiation sources

Exposure of the skin to UV radiation can lead to a local infiltration of neutrophils. Not much is known on whether the infiltration of neutrophils in the irradiated skin is UV source dependent. In this study we compared different UV sources (solar-simulated radiation [SSR], narrowband [NB]-UVB, broadband [BB]-UVB and UVA1) in their potency to induce neutrophil infiltration in normal human skin after exposure to two times the minimal erythema dose of UV radiation. Biopsies were collected from irradiated buttock skin 6 and 24 h after irradiation and from nonirradiated skin. The presence, distribution and amount of skin-infiltrated neutrophils were determined using immunohistochemical staining. Analysis revealed that SSR was most effective in inducing neutrophil infiltration. NB-UVB gave a neutrophil influx pattern similar to that seen with SSR but in smaller numbers. BB-UVB and UVA1 were far less potent in inducing neutrophil infiltration compared with SSR or NB-UVB. Our findings indicate that neutrophil infiltration in the UV-irradiated skin is UV source dependent. When the spectra emitted by the different UV sources were compared UVB seemed to be more effective than UVA in inducing neutrophil infiltration. Furthermore, our results suggest that longer wavelengths within the UVB range are mostly responsible for the infiltration of neutrophils in the UV-irradiated skin.     

Tanning in Human Skin Types II and III Offers Modest Photoprotection Against Erythema

We have investigated the photoprotective properties of tanning using erythema as an endpoint. Previously unexposed buttock skin sites of 16 young, healthy adults (8 skin type II, and 8 skin type III) were exposed daily (Mon-Fri) for 2 weeks to 0.5 and 0.75 minimal erythema doses (MED) of solar-simulated radiation (SSR). Erythema and melanin levels were assessed daily both visually and quantitatively using a reflectance device. One week after the last tanning treatment, MED reassessments were made on pretreated sites and on adjacent nontreat-ed sites, including sites from which stratum corneum was removed by tape stripping. Compared to skin type II, similar daily SSR treatments produced less erythema and more evident tanning in skin types III. Independent of skin type, all volunteers showed an increased MED value when assessed on the 0.75 MED- and 0.5 MED-treated sites compared to the MED value assessed on adjacent untreated sites. We express any increase in MED as an induced protection factor (IPF), i.e. (MED post-tan/MED pre-tan). Our data show mean IPF of 1.4 and of 2.1 in the 0.5 and 0.75 MED-treated sites respectively, in skin types II. Similar values were obtained in skin types III with IPF of 1.5 and 2.3 for the 0.5 and 0.75 MED-treated sites, respectively. In all cases, removal of the stratum corneum lowered the IPF by about 20%. Our results show that SSR-induced melanogenesis, whether in skin type II or III, offers only moderate protection against erythema and suggest that SSR-induced stratum corneum thickening affords less photoprotection than tanning.     

Ultrasound measurements of skin thickness after UV exposure: a feasibility study

High-frequency ultrasound images were used to measure the thickness of the dermis and epidermis of four human subjects. These measurements were performed before and after a single exposure to ultraviolet radiation (UV). Doses ranging from 0.5 to 3 minimal erythema doses (MED) were delivered to the skin of the back of four human subjects, and thickness measurements were made over a period of 16 days. We found: (1) exposures > or = 2 MED caused a 10-30% increase in the thickness of the dermis-epidermis layer; (2) the thickening response was not always in direct proportion to the UV dose; (3) maximum thickening response time was 48 h for the 2.8-3.0 MED exposure levels; (4) "diffusion" or spreading of the thickening response to neighboring areas occurred in some cases, as far as 4 cm from the exposed region (center-to-center), with changes ranging from 12% to 17%; (5) decreased thickness of the dermis-epidermis layer of up to 12% was observed for 3 out of 4 of the subjects.     

Noninvasive Optical Imaging of UV‐Induced Squamous Cell Carcinoma in Murine Skin: Studies of Early Tumor Development and Vitamin D Enhancement of Protoporphyrin IX Production

Better noninvasive techniques are needed to monitor protoporphyrin IX (PpIX) levels before and during photodynamic therapy (PDT) of squamous cell carcinoma (SCC) of the skin. Our aim was to evaluate (1) multispectral fluorescent imaging of ultraviolet light (UV)‐induced cancer and precancer in a mouse model of SCC and (2) multispectral imaging and probe‐based fluorescence detection as a tool to study vitamin D (VD) effects on aminolevulinic acid (ALA)‐induced PpIX synthesis. Dorsal skin of hairless mice was imaged weekly during a 24‐week UV carcinogenesis protocol. Hot spots of PpIX fluorescence were detectable by multispectral imaging beginning at 14 weeks of UV exposure. Many hot spots disappeared after cessation of UV at week 20, but others persisted or became visible after week 20, and corresponded to tumors that eventually became visible by eye. In SCC‐bearing mice pretreated with topical VD before ALA application, our optical techniques confirmed that VD preconditioning induces a tumor‐selective increase in PpIX levels. Fluorescence‐based optical imaging of PpIX is a promising tool for detecting early SCC lesions of the skin. Pretreatment with VD can increase the ability to detect early tumors, providing a potential new way to improve efficacy of ALA‐PDT.     

Interaction of UVB-absorbing sunscreen ingredients with cutaneous molecules may alter photoimmune protection.

Studies of the photoimmunoprotective properties of sunscreens have produced disparate results. In this study in hairless mice, we compared two UVB absorbers, 2-ethylhexyl-p-methoxycinnamate (2-EHMC) and octyl-N-dimethyl-p-aminobenzoate (o-PABA), individually formulated in a common base lotion with a sunburn protection factor of 6. We measured their capacity to protect against suppression of the contact hypersensitivity (CHS) induced by three daily exposures of the dorsum to 6x the minimal erythemal/edematous dose (MED) of solar-simulated UV radiation (SSUV), in comparison with base lotion-treated mice exposed to 3 x 1 MED of SSUV. All treatments produced a similar minimal erythema. CHS was equally suppressed in mice irradiated through o-PABA and base lotion, but the suppression was significantly reduced in mice irradiated through 2-EHMC. Neither UVB absorber inhibited the epidermal photoisomerization to the immunosuppressive mediator, cis-urocanic acid. However, when mice were treated with exogenous cis-urocanic acid topically on the dorsum, but not when injected subcutaneously on the abdomen, suppression of CHS was observed in o-PABA- and base lotion-treated mice, but not in 2-EHMC-treated mice. Thus, the enhanced immunoprotection in mice irradiated through 2-EHMC apparently resulted from the direct inactivation of epidermal cis-urocanic acid by 2-EHMC. We conclude that comparative assessment of photoimmunoprotection by UV absorbers requires SSUV, erythemally matched exposures and consideration of potential interactions with cutaneous molecules.     

Optical coherence tomography in biomedical research

Optical coherence tomography (OCT) is a noninvasive, high-resolution, interferometric imaging modality using near-infrared light to acquire cross-sections and three-dimensional images of the subsurface microstructure of biological specimens. Because of rapid improvement of the acquisition speed and axial resolution of OCT over recent years, OCT is becoming increasingly attractive for applications in biomedical research. Therefore, OCT is no longer used solely for structural investigations of biological samples but also for functional examination, making it potentially useful in bioanalytical science. The combination of in vivo structural and functional findings makes it possible to obtain thorough knowledge on basic physiological and pathological processes. Advanced applications, for example, optical biopsy in visceral cavities, have been enabled by combining OCT with established imaging modalities. This report gives an outline of the state of the art and novel trends of innovative OCT approaches in biomedical research in which the main focus is on applications in fundamental research and pre-clinical utilization.     

Adaptation of the human skin by chronic solar-simulating UV irradiation prevents ultraviolet-B irradiation-induced rise in serum C-reactive protein levels

Exposure of the skin to UV radiation induces local inflammation. We hypothesized that inflammation induced by erythemal UV-B irradiation could elevate levels of serum C-reactive protein (CRP) and that suberythemal repeating doses of solar-simulating UV radiation (SSR) would produce photoadaptation to such inflammation. Separation-free high-sensitivity assays of CRP show an increase by 42% (P = 0.046) in CRP concentrations in healthy human subjects 24 h after a 3 minimal erythemal dose (MED) dose of UV-B delivered onto a 100 cm2 skin area. Preceding daily suberythemal doses of whole-body SSR for 10 or 30 consecutive days completely prevented the CRP increase. UV-B-induced skin erythema was partially attenuated by 30 preceding days of SSR only (P = 0.00066). After 10 daily SSR doses, the mean baseline CRP concentrations (0.24 +/- 0.21 mg/L) declined by 35% (P = 0.018). Using high-sensitivity analysis of serum CRP as the endpoint marker for cutaneous inflammation, we show that acute exposure of even a relatively small skin area to erythemal UV-B induces skin inflammation detectable also at the systemic level and that photoadaptation by preceding repeating suberythemal doses of SSR reduces signs of inflammation. Our data complement the view given by previous studies in that local photoadaptation also has systemic manifestations.