Dominique Moyal

Broad-spectrum sunscreens provide better protection from solar ultraviolet–simulated radiation and natural sunlight–induced immunosuppression in human beings

BACKGROUND It is well established that ultraviolet (UV) radiation induces immunomodulatory effects that may be involved in skin cancer. Recent studies have shown that UVA (320-400 nm) and UVB (290-320 nm) radiation are immunosuppressive. As a result, sunscreens, which mainly absorb UVB, may be less effective in preventing UV radiation-induced immunosuppression than broad-spectrum products. OBJECTIVE We sought to study the effects of UVA exposure on human delayed-type hypersensitivity (DTH) response and compare the efficacy of sunscreens having different levels of sun-protection factor (SPF) and UVA protection against both solar-simulated radiation and outdoor real-life sunlight exposure conditions. METHODS DTH was assessed using a kit which includes 7 recall antigens that most of the participants encountered during childhood immunization. Evaluation of DTH test response was made 48 hours after test application before and after UV exposure with or without sunscreens. RESULTS In unprotected participants, the response to DTH tests was significantly reduced irrespective of UV types of exposure (full-spectrum UVA, long UVA, solar-simulated radiation). A UVB sunscreen failed to protect from solar-simulated radiation-induced immunosuppression. In contrast, a broad-spectrum sunscreen with the same SPF but providing a high protection in the UVA range significantly reduced local UV-induced immunosuppression and prevented the distant effects. In the outdoor study, as compared with DTH responses obtained before sun exposure, no alteration of immune response was detected when the skin was protected by a broad-spectrum sunscreen having a high protection level in the UVA (SPF 25, UVA protection factor 14). Conversely a broad-spectrum sunscreen with lower protection against UVA (SPF 25, UVA protection factor 6) failed to prevent UV-impaired response. LIMITATIONS These results have been obtained after repeated exposure. Additional experiments obtained under acute exposure are in progress. CONCLUSION These findings clearly demonstrated the role of UVA in the induction of photoimmunosuppression together with the need for sunscreen products providing efficient photoprotection throughout the entire UV spectrum.

Photodamage to human skin by suberythemal exposure to solar ultraviolet radiation can be attenuated by sunscreens: a review

The effects of acute or repeated suberythemal solar ultraviolet radiation (UVR) exposure on human skin have been insufficiently investigated. Such exposure almost certainly has important long‐term consequences that include skin ageing and skin cancer. This review summarizes the published data on the biological effects of suberythemal exposure using a wide range of clinical, cellular and molecular endpoints, some of which may be considered as biomarkers for skin cancer and photoageing. We also include some recent unpublished results from our laboratories. The effects of UVA (320–400 nm), UVB (290–320 nm) and total solar UVR (290–400 nm) are compared. We demonstrate that avoiding sunburn does not prevent many indicators of cutaneous biological damage and that use of low sun protection factor (SPF) sunscreen can inhibit much of the damages induced by suberythemal exposure to UVR. However, even when applied correctly, sunscreen use will result in suberythemal exposure. The degree and spectral quality of such exposure will depend on the SPF and absorption spectrum of the sunscreen, but nonetheless it may contribute to cumulative photodamage. This review may help to determine the level of photoprotection required in sunscreens and daily use products, as well as the ideal ratio of UVB/UVA protection, to improve long‐term photoprotection outcomes.

MEXORYL SX : A BROAD ABSORPTION UVA FILTER PROTECTS HUMAN SKIN FROM THE EFFECTS OF REPEATED SUBERYTHEMAL DOSES OF UVA

There is now considerable evidence that chronic UVA exposure induces damage in animal and human skin; however, little is known about UVA protection of human skin. The aim of this study is to evaluate the efficacy of Mexoryl SX, a broad UVA absorber (lamada max = 345 nm) against UVA-induced changes in human skin. The regimen of UVA exposure (13 weeks with increasing suberythemal doses) induces intense pigmentation with no erythema. Skin hydration and elasticity decrease, whereas total skin thickness, assessed by echography, remains unchanged. Irradiated epidermis reveals a significant thickening of the stratum corneum, an absence of hyperplasia and an increase in the expression of the protective iron-storage protein ferritin. No significant alterations are seen using antisera against type IV collagen or laminin, suggesting that the dermal-epidermal junction (DEJ) is mainly preserved. In dermis, enhanced expression of tenascin is seen just below the DEJ but type I procollagen, which is localized at the same site, is unaltered. Although we are unable to visualize any changes in elastic network organization using Luna staining or specific antiserum directed against human elastin, we notice an increased deposition of lysozyme or alpha-1 antitrypsin on elastin fibres. Mexoryl SX (5%) efficiently prevents these alterations. Thus, these results suggest that UVA photoprotection can prevent early putative alterations leading to photoageing.

Alterations in human epidermal Langerhans cells by ultraviolet radiation: quantitative and morphological study

Summary Background Ultraviolet (UV) exposure of human skin induces local and systemic immune suppression. This phenomenon has been well documented when UVB radiation (290–320 nm) is used. The mechanism is thought to involve Langerhans cells (LCs), the epidermal dendritic cells that play a crucial role in antigen presentation. A variety of studies have clearly demonstrated that UVB radiation decreases LC density and alters their morphology and immunological function, but little is known about the effects of the entire UV spectrum (ultraviolet solar simulated radiation, UV‐SSR or UVB + UVA) or UVA (320–400 nm) radiation alone.

Sunscreens containing the broad-spectrum UVA absorber, Mexoryl® SX, prevent the cutaneous detrimental effects of UV exposure : a review of clinical study results

Background: UVA exposure of human skin mainly produces reactive oxygen species (ROS) leading to DNA, cell and tissue damage. It alters immune function, pigmentation and it is certainly responsible for a large part of photoaging changes. Moreover UVA is implicated in the etiology of several photodermatoses. As a consequence, to provide adequate protection, sunscreens or skin care products for daily use protective products need UVA absorbers combined with UVB ones.

Determination of UVA protection factors using the persistent pigment darkening (PPD) as the end point (part 1) calibration of the method

Background/Aims: The accuracy and reliability of any method to assess the UVA protection effectiveness of sunscreens needs to be demonstrated. The aim of the present study was to calibrate the effectiveness of a biological end point (Persistent Pigment Darkening, PPD) to assess UVA photoprotection.

Accumulated p53 protein and UVA protection level of sunscreens

Nuclear p53 expression is a sensitive parameter for the detection of ultraviolet (UV)‐induced skin damage, and it has been used as an endpoint to evaluate the effectiveness of sunscreens. In this study, we compared the protection provided by two sunscreens having identical sun protection factors (SPF) but different UVA protection factors (UVA‐PF) measured by the persistent pigment darkening method (PPD). The SPF of the sunscreens was 7 and the UVA‐PF were respectively 7 and 3. Nuclear p53 protein was quantified in human skin biopsies treated with sunscreens and exposed 8 times to 5 MED of solar simulated radiation (SSR). The results showed that both sunscreens offered only partial protection against the increased expression of nuclear p53 protein induced by repetitive SSR exposures. However, a significantly lower level of p53‐positive cells was found in areas protected with the sunscreen having the higher UVA‐PF compared to the other sunscreen protected areas. In order to verify whether the difference in efficacy of these products was due to the difference in UVA absorption capacity, we quantified epidermal p53 protein accumulation after 8 exposures to either UVA (320–400 nm) or UVA1 (340–400 nm). We showed that as with SSR, repetitive exposures to 12.5 and 25 J/cm2 of UVA or UVA1 induced a significant increase in p53‐positive cells in the human epidermis. These results confirmed that SPF determined on the basis of an acute erythemal reaction does not predict the level of protection against cumulative damage. They also showed that the protection provided by two sunscreens with different UVA protection factors is different (based on nuclear p53 protein accumulation), and that the PPD method can distinguish varying levels of sunscreen efficacy against UVA‐induced cell damage.

UVA protection efficacy of sunscreens can be determined by the persistent pigment darkening (PPD) method. (Part 2).

Background: The UVA‐induced Persistent Pigment Darkening (PPD) in vivo has been proposed as an end point for the evaluation of UVA protection.

Protection of skin biological targets by different types of sunscreens

In vitro and in vivo studies provide a body of evidence that adequate protection of the skin against ultraviolet (UV)‐induced damage requires photostable broad‐spectrum sunscreens with a proper level of UVA protection. UVA alone and UV solar simulated radiation (SSR) induce DNA lesions in keratinocytes and melanocytes as reflected by the comet assay and p53 accumulation. UVA and SSR impair the immune system as shown by significant alteration of Langerhans cells and inhibition of contact hypersensitivity response to chemical allergens and delayed‐type hypersensitivity response to recall antigens. Any of these detrimental effects is more efficiently prevented by sunscreens with a higher level of protection in the UVA range. The involvement of UVA (fibroblast alteration, increased metalloproteinase expression) and the pivotal need for well‐balanced UVA/UVB sunscreens were further demonstrated using reconstructed three‐dimensional skin models.

Efficacy of broad‐spectrum sunscreens against the suppression of elicitation of delayed‐type hypersensitivity responses in humans depends on the level of ultraviolet A protection

Abstract: Sunscreens have been designed to protect against sunburn and their efficacy has, therefore, been labeled by the so‐called sun protection factor (SPF). Although this value is well determined using a standardized protocol and it affords a good evaluation of the protection against erythema it may be inadequate to provide a relevant measurement of efficacy against other biologic damages. This is particularly true when action spectra and threshold dose are different from those of erythema. In the case of ultraviolet (UV)‐induced immune suppression, the action spectrum is not known, so it cannot be asserted that SPF may accurately predict the level of protection against this endpoint. We addressed this issue by measuring in human volunteers the ability of two broad‐spectrum SPF 15 sunscreens with different ultraviolet A (UVA) protection levels, to prevent the alteration of the efferent phase of the local delayed‐type hypersensitivity (DTH) response to recall antigens (Multitest Pasteur/Mérieux, Lyon, France) after acute solar‐simulated UV exposure. We first determined the ultraviolet radiation (UVR) dose needed to induce a significant DTH inhibition in several groups of 15 volunteers. Two minimal erythemal doses (2 MED) were found to be the minimal immunosuppressive dose (MISD). As a result, the immune DTH response is reduced in average by 36%. The lower doses tested (0.5 and 1 MED) were ineffective. Sunscreen‐treated groups were exposed to either 1 or 2 MED × SPF doses. As expected, no alteration in DTH response was observed in the groups exposed to 1 MED × SPF whatever the sunscreen applied. In contrast, after exposure to 2 MED × SPF, the DTH response remained unaltered in the group pretreated with the sunscreen product with the higher protection in the UVA range but was significantly suppressed by 55.7% in the group pretreated with sunscreen with a much lower protection in the UVA range. These data suggest that SPF may not be sufficient to predict the ability of sunscreens to protect from UV‐induced immune suppression. Determining the level of UVA protection is particularly needed, as UVA seems to have a relatively low contribution to erythema but is highly involved in immunosuppression.