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Epidermal melanin reduces some effects of UV radiation, the major cause of skin cancer. To examine whether induced melanin can provide protection from sunburn injury, 65 subjects completed a trial with the potent synthetic melanotropin, [Nle4-D-Phe7]-α-melanocyte-stimulating hormone ([Nle4-D-Phe7]-α-MSH) delivered by subcutaneous injection into the abdomen at 0.16 mg/kg for three 10-day cycles over 3 months. Melanin density, measured by reflectance spectroscopy, increased significantly in all [Nle4-D-Phe7]-α-MSH-treated subjects. The highest increases were in volunteers with lowest baseline skin melanin levels. In subjects with low minimal erythemal dose (MED) skin type, melanin increased by an average of 41% (from 2.55 to 3.59, P<0.0001 vs placebo) over eight separate skin sites compared with only 12% (from 4.18 to 4.70, P<0.0001 vs placebo) in subjects with a high-MED skin type. Epidermal sunburn cells resulting from exposure to 3 MED of UV radiation were reduced by more than 50% after [Nle4-D-Phe7]-α-MSH treatment in the volunteers with low baseline MED. Thymine dimer formation was also shown to be reduced by 59% (P=0.002) in the epidermal basal layer. This study has shown for the first time the potential ability of a synthetic hormone that augments melanin production to provide photoprotection to people who normally burn in direct sunlight.Journal of Investigative Dermatology (2006) 126, 1869–1878. doi:10.1038/sj.jid.5700317; published online 8 June 2006 [ABSTRACT FROM AUTHOR]

Background/purpose: This study aimed to determine the relationship between various measures of constitutive skin pigmentation and erythema caused by solar-simulated UV (ssUV), 290 and 310 nm UV. Methods: Skin pigmentation was assessed clinically by skin typing as well as objectively by measurement of the melanin index (MI) by reflectance spectroscopy. Subjects having Fitzpatrick skin types I–IV were exposed to graded doses of ssUV and either narrowband 310 nm ( n=70) or 290 nm ( n=69) UV, and assessed 24 h after exposure. Minimal erythema dose (MED) was assessed visually as the lowest dose that caused minimally perceptible erythema. Susceptibility to further development of erythema with higher exposure doses was measured by the gradient of erythema dose–response curves. This was determined by linear regression using reflectance spectrometry data beyond the MED. Results: Although there was considerable variation within each skin type, MI and ssUV MED increased with increasing Fitzpatrick skin type. MI correlated with ssUV MED and 310 nm UV MED, but not 290 nm UV MED. There was also a significant negative correlation between MI and erythema dose–response gradients caused by ssUV, 310 and 290 nm UV. Conclusion: Melanin situated near the basal epidermis may not protect from the initial development of threshold erythema caused by 290 nm UV because it penetrates poorly past the stratum corneum and is not well absorbed by melanin in vivo compared with 310 nm UV. Higher erythemal 290 nm UV doses may reach basal epidermal melanin, which may then afford protection against further 290 nm UV erythema. [ABSTRACT FROM AUTHOR]

Solar-simulated ultraviolet radiation (ssUV) suppresses immunity in humans. The ultraviolet B (UVB) waveband is recognized as immunosuppressive; however the relative significance of UVA to ssUV immunosuppression is unknown. We created dose and time–response curves for UVB-, UVA-, and ssUV-induced suppression of memory immunity to nickel in humans. UVB caused immunosuppression within 24 h. UVA immunosuppression required 48 h and was normalized by 72 h. UVB alone accounts for ssUV immunosuppression at 24 h, but both UVB and UVA contributed at 48 h. By 72 h neither waveband accounted for ssUV immunosuppression. An interaction between these wavebands was therefore the major contributor. To confirm this dose–response curves were used to determine immune protection factors (IPF) for sunscreens with nickel challenge 72 h following ssUV. A sunscreen with good UVA protection had an IPF twice that of a poor UVA protector, despite providing similar protection from sunburn. Thus UVA was a major contributor to ssUV-induced immunosuppression at 72 h but only with the cooperation of UVB. Hence, UVB initiates immunosuppressive signals within 24 h, followed by UVA at 48 h, then an interaction between UVB and UVA. By 72 h following ssUV exposure, neither UVB nor UVA, but an interaction between them is the major cause of sunlight-induced immunosuppression. [ABSTRACT FROM AUTHOR]

We hypothesized that a substantial portion of the mutagenic alterations produced in the basal layer of human skin by sunlight are induced by wavelengths in the UVA range. Using laser capture microdissection we examined separately basal and suprabasal keratinocytes from human skin squamous cell carcinomas and premalignant solar keratosis for both UVA- and UVB-induced adduct formation and signature mutations. We found that UVA fingerprint mutations were detectable in human skin squamous cell carcinomas and solar keratosis, mostly in the basal germinative layer, which contrasted with a predominantly suprabasal localization of UVB fingerprint mutations in these lesions. The epidermal layer bias was confirmed by immunohistochemical analyses with a superficial localization of cyclobutane thymine dimers contrasting with the localization of 8-hydroxy-2'-deoxyguanine adducts to the basal epithelial layers. If unrepaired, these adducts may lead to fixed genomic mutations. The basal location of UVA- rather than UVB-induced DNA damage suggests that longer-wavelength UVR is an important carcinogen in the stem cell compartment of the skin. Given the traditional emphasis on UVB, these results may have profound implications for future public health initiatives for skin cancer prevention. [ABSTRACT FROM AUTHOR]

Topical application of N G -methyl-L-arginine and 2,2′-dipyridyl were used to examine the respective roles of nitric oxide and reactive oxygen species in solar-simulated ultraviolet radiation-induced immunosuppression in humans in vivo . Immunosuppression was studied using a nickel contact hypersensitivity recall model. Ultraviolet radiation dose–responses were generated to determine the extent to which N G -methyl-L-arginine and 2,2′-dipyridyl affected the immune response. N G -methyl-L-arginine but not 2,2′-dipyridyl protected the immune system from ultraviolet radiation-induced suppression. Both N G -methyl-L-arginine and 2,2′-dipyridyl inhibited nitrite production. Nitrite is a degradation product of peroxynitrite, a cytotoxic mediator resulting from reactions between nitric oxide and reactive oxygen species. This suggests that nitric oxide, not its downstream product peroxynitrite, was likely to be responsible for solar-simulated ultraviolet radiation-induced immunosuppression. In contrast, both nitric oxide and reactive oxygen species were mediators of solar-simulated ultraviolet radiation-induced apoptosis and loss of dendritic S-100+ cells (probably Langerhans cells) from the epidermis. It is likely that different mechanisms are involved in these ultraviolet-induced endpoints and that events in addition to Langerhans cell depletion are important for local immune suppression to recall antigens in humans. Understanding the mechanisms of cutaneous ultraviolet-induced oxidative stress will assist in the future design of novel products that protect skin from photoaging and skin cancer. [ABSTRACT FROM AUTHOR]

Sunscreens have been advocated as an important means of preventing skin cancer. Ultraviolet radiation induced immunosuppression is recognized as an important event in skin cancer development, yet the effectiveness of sunscreens in protecting the human immune system from ultraviolet radiation (i.e. ultraviolet radiation) is still unclear. The only currently accepted method of sunscreen rating is the sun protection factor system based on the prevention of erythema. We determined immune protection factors for six commercially available sunscreens using a nickel contact hypersensitivity model in humans. Both sun protection factor and immune protection factor testing was performed using the same solar simulated ultraviolet radiation source and dose–responses were used to determine endpoints both with and without sunscreens. We found that the immune protection factor did not correlate with the sun protection factor; however, immune protection factor was significantly correlated to the ultraviolet A protective capability of the sunscreens, indicating that sunscreen protection from ultraviolet A is important for the prevention of ultraviolet immunosuppression, when there is constant ultraviolet B protection. We recommend that sunscreens should be rated against their immune protective capability to provide a better indication of their ability to protect against skin cancer. [ABSTRACT FROM AUTHOR]

This study investigates the relative effects of low-dose solar-simulated ultraviolet, ultraviolet A, and ultraviolet B radiation on the elicitation of contact hypersensitivity to nickel in nickel-allergic volunteers. A xenon arc lamp with changeable filters was used to irradiate groups of volunteers daily, on separate areas of their lower backs, with both solar-simulated ultraviolet (ultraviolet B, ultraviolet AII + ultraviolet AI) and ultraviolet A (same ultraviolet AII content but twice the ultraviolet AI as the solar-simulated ultraviolet spectrum) for 1 and 2 d; 3, 4, and 5 d; and from 1 to 4 wk. A fourth group was irradiated for 1–5 d with the ultraviolet B component of solar-simulated ultraviolet. Following the final irradiation in each group, nickel-containing patches were applied to both ultraviolet-treated sites and adjacent, unirradiated control sites. Erythema caused by nickel contact hypersensitivity at each site was quantitated 72 h later with a reflectance erythema meter. By comparing the nickel reactions of irradiated and unirradiated skin, ultraviolet immunosuppression was assessed with the different spectra and durations of ultraviolet exposure. We found significant immunosuppression with daily doses of ultraviolet B and ultraviolet A equivalent to approximately 6 min of summer sun exposure, and that ultraviolet A and ultraviolet B exerted their maximal immunosuppressive effects at different times. Solar-simulated ultraviolet-induced immunosuppression was significant after one exposure, near-maximal after two exposures and remained elevated thereafter. Ultraviolet B-induced immunosuppression was lower than that induced by solar-simulated ultraviolet, but followed a similar time-course. In contrast, ultraviolet A-induced immunosuppression was transient, peaking after three exposures. Immune responses returned towards normal with subsequent ultraviolet A exposure, suggesting that an adaptive mechanism may prevent immunosuppression by... [ABSTRACT FROM AUTHOR]

This study investigates the influence of skin colour and minimal erythema dose (MED) on the in vivo determination of sunscreen sun protection factors (SPFs). The MEDs of groups of 10–20 subjects were measured on the lower back with a 1000-W solar-simulated xenon arc lamp. Five sunscreens, with commercially measured SPFs ranging from 4 to 30 + were then tested on the different groups, and their SPFs were correlated with volunteers' MEDs. We found that the sunscreens had higher SPF values when tested on subjects with lower MEDs and paler skin. The SPF values obtained with our ultraviolet (UV) source were lower than the SPF values reported with commercially used solar simulators. We conclude that while SPF tests with artificial UV sources and pale-skinned volunteers can and should be used to rank the efficacy of various sunscreens in preventing sunburn, they should not be interpreted as measures of a sunscreen's absolute level of sun protection. Factors such as the differences in skin colour and MED between subjects used for SPF testing and the general population, the spectral differences between sunlight and artificial UV, as well as the tendency of the public to apply only small amounts of sunscreen and to re-apply it infrequently, mean that laboratory and sunlight SPFs may be markedly different. [ABSTRACT FROM AUTHOR]

This study compares the ability of two ultraviolet (UV) B-absorbing sunscreens, 2-ethyihexyl p-me- thoxycinnamate (2-EHMC) and 2-ethylhexyl p-ami- nobenzoate (Padiniate O), and two physical sun- screens, microfine titanium dioxide (MTD) and zinc oxide, to protect the skin immune system from chronic (4 weeks) solar-simulated UV irradiation. Mice were exposed to suberythemal doses of UV before assessing local and systemic immunosuppression and tolerance to a contact sensitizer. Using a UV protocol that induced local but not systemic immunosuppression or tolerance in BALB/c mice, it was shown that Padimate O made the immunosuppression worse, whereas 2-EHMC and MTD protected the immune system. When the cumulative dose was increased by 12.7%, causing systemic immunosuppression and tolerance, none of the sunscreens protected from inimunosuppression, but 2-EHMC provided partial, and MTD gave complete protection from tolerance. To examine this apparent lack of protection from systemic immunosuppression, C3H/HeJ mice were used. These mice had a minimal erythema dose similar to that of the BALB/c mice but were systemically immunosuppressed, with only 44% of the UV dose required to immunosuppress BALB/c mice. 2-EHMC provided some protection, whereas MTD provided complete protection from systemic immunosuppression in C3H/HeJ mice. Hence, sunscreens can protect from local and systemic immunosuppression, although this protection is limited and is not related to the sun protection factor of the sunscreens or the minimal erythema dose of the mouse strain. Instead, protection seems to be related to the sunscreens' having a broad absorption spectrum. [ABSTRACT FROM AUTHOR]

Focuses on the efficacy of sunscreen to prevent immunosuppression. Use of sunscreens to protect from erythema; Assessment on the immunoprotective ability of sunscreens; Dependency of immune protection of the sunscreens upon absorption of ultraviolet-A and -B.

This study investigates the extent to which sun- screens protect humans from ultraviolet (UV)-radiation-induced immunosuppression. In the presence of solar-simulated UV, three sunscreens with differing UVA transmission were assessed for their ability to protect the contact hypersensitivity (CHS) response to nickel of 16 nickel-allergic subjects. The sunscreens contained 2-ethylhexyl para-methoxycin- namate (cinnamate), cinnamate with oxybenzone, or cinnamate with zinc oxide, respectively. All had sun protection factors of 10 and hence inhibited UV erythema to similar extents. Volunteers were irradiated on their backs with suberythemal UV daily for 5 d after application of the sunscreens and theft base lotion to different sites. Nickel-containing patches were then applied to both UV-treated sites and adjacent, unirradiated control sites. Erythema caused by nickel CHS at each site was quantitated 72 h later with a reflectance erythema meter. In comparison of the nickel reactions of irradiated and unirradiated skin, there was 35% mean immunosuppression in unprotected UV-treated skin. Significant immuno- suppression also occurred at sites irradiated through the narrow-spectrum cinnamate-only sunscreen but was prevented by the two broad-spectrum sun- screens. To determine whether UV-induced suppression of the nickel response is specific for cell-mediated immunity or reflects suppression of nonspecific inflammation, a further 16 subjects were patch-tested with a skin irritant, sodium lauryl sulfate (SLS), following a sunscreen and irradiation protocol identical to that of the nickel volunteers. UV had no significant effect on SLS responses. We conclude that nickel patch testing is a valid means of assessing UV-induced immunosuppression in humans and that even with suberythemal UV, immune protection was provided only by sunscreens filtering both UVA and UVB. [ABSTRACT FROM AUTHOR]

This study compares the ability of two commonly used sunscreens--octyl dimethyl para-aminobenzoate (Padimate O) and 2-ethylhexyl-p-methoxycinnamate (2-EHMC) to protect Langerhans cells (LC), Thy-1+ dendritic epidermal cells (Thy-1+dEC), and local contact sensitivity (CS) from the effects of ultraviolet (UV) light. Chronic exposure of mice 5 d per week for 4 Weeks with an intermediate dose of solar-simulated sunlight from which any UVC had been filtered reduced the LC and Thy-1+ dEC density of murine epidermis. This irradiation procedure was designed to simulate closely the daily exposure of humans to sunlight. This effect on LC and Thy-1+dEC occurred in both albino and pigmented mice that develop a tan during the irradiation procedure, indicating that a tan does not protect these cells from the effects of UV light. Sunscreen preparations with Padimate O and 2-EHMC, both of which also contained benzophenone-3, as well as Padimate O or 2-EHMC in organic solvent, inhibited UV light from depleting LC from the epidermis of both mouse strains. Padimate O and 2EHMC in organic solvent were used to ensure that these were the active ingredients in the sunscreen preparations. In contrast to the effects on LC, Padimate O, but not 2-EHMC, protected Thy-l+dEC from UV exposure in both mouse strains, but neither protected against the development of local immunosuppression using a contact sensitivity model. Thus, even in a mouse strain that is sensitive to UV-induced immunosuppression, local immunosuppression can occur in the presence of normal densities of LC and Thy-l+ dEC. [ABSTRACT FROM AUTHOR]

There has been much speculation as to the role of Langerhans cells (LC) in the induction of anti-tumor immunity. Whereas there is considerable circumstantial evidence that disruptions in the density and function of these cells during the early stages of ultraviolet (UV) light- and chemical carcinogen-induced carcinogenesis may be important for enabling developing neoplasms to escape immune destruction, the role of the large number of these cells found infiltrating developed skin tumors is less clear. To investigate this we have compared the LC density infiltrating transplanted non-immunogenic and immunogenic UV-induced murine tumors as well as LC in the epidermis overlying the tumors. Whereas two non-immunogenic tumor lines attracted large numbers of Ia+ dendritic cells, an immunogenic tumor line did not. Similar results were obtained whether the tumors were transplanted into syngeneic immunocompetent or athymic immunodeficient mice. Hence, there was no relationship between tumor immunogenicity or host immunocompetence and Ia+ dendritic cell density. Furthermore, there was no correlation with the pattern of T-cell infiltration of the tumors or CD4/CD8 cell ratio. Our results also indicate that whereas UV light decreased Ia+ cell density, both in the epidermis and the tumors, it did not inhibit the tumors from attracting Ia+ dendritic cells. Thus, the Ia+ dendritic cells infiltrating skin tumors are unlikely to indicate a host immune response to the tumor, but are more likely to be attracted by tumor-derived cytokines. [ABSTRACT FROM AUTHOR]

UV radiation-induced immunosuppression augments cutaneous carcinogenesis. The incidence of skin cancer continues to increase despite increased use of sunscreens, which are less effective at preventing immunosuppression than sunburn. Using the Mantoux reaction as a model of skin immunity, we investigated the effects of solar-simulated (ss) UV and its component UVA and UVB wavebands and tested the ability of topical nicotinamide to protect from UV-induced immunosuppression. Healthy, Mantoux-positive volunteers were UV-irradiated on their backs, with 5% nicotinamide or vehicle applied to different sites in a randomized, double-blinded manner. Subsequent Mantoux testing at irradiated and adjacent unirradiated sites enabled measurement of UV-induced immunosuppression with and without nicotinamide. Suberythemal ssUV caused significant immunosuppression, although component UVB and UVA doses delivered independently did not. Men were immunosuppressed by ssUV doses three times lower than those required to immunosuppress women. This may be an important cause of the higher skin cancer incidence and mortality observed in men. Topical nicotinamide prevented immunosuppression, with gene chip microarrays suggesting that the mechanisms of protection may include alterations in complement, energy metabolism and apoptosis pathways. Nicotinamide is a safe and inexpensive compound that could be added to sunscreens or after-sun lotions to improve protection from immunosuppression. immunosuppression.JID JOURNAL CLUB ARTICLE: For questions, answers, and open discussion about this article, please go to http://network.nature.com/group/jidclubJournal of Investigative Dermatology (2008) 128, 447–454; doi:10.1038/sj.jid.5701058; published online 20 September 2007 [ABSTRACT FROM AUTHOR]

The effects of low dose ultraviolet (UV) radiation on delayed type hypersensitivity responses to tuberculin purified protein derivative were investigated in 17 healthy, Mantoux‐positive volunteers. Suberythemal and erythemal doses of solar simulated UV from a fluorescent lamp source were delivered to the subjects’ lower backs daily for five consecutive days. Mantoux testing with intradermally injected purified protein derivative was then performed at both the irradiated sites and an adjacent, unirradiated site, and the Mantoux induced erythema was quantitated 72 h later with a reflectance erythema meter. In comparison with the unirradiated Mantoux sites, Mantoux induced erythema was significantly reduced at the irradiated test sites. In six subjects, we compared the effects of chronic versus short term UV irradiation on the Mantoux reaction. These volunteers were irradiated on one side of their lower backs with the 5 d UV protocol, and on the other side of their backs for 4 or 5 wk. In all but one subject, the short irradiation protocol induced greater suppression of Mantoux responses than prolonged UV exposure. We conclude that even suberythemal doses of UV significantly reduce delayed type hypersensitivity responses to purified protein derivative, and that an adaptive mechanism appears to counteract the immunosuppressive effects of chronic irradiation. [ABSTRACT FROM AUTHOR]