Are broad-spectrum sunscreens necessary for immunoprotection?

A sunscreen is labelled with its sun protection factor (SPF). This is a measure of the protection it aiords against sunburn after a single exposure of solar simulating radiation (SSR): nothing more and nothing less. Calculations based on the action spectrum (wavelength dependence) for erythema (sunburn) and solar emission spectra show that the small UVB (B5%) component of solar UVR accounts for the vast majority (480%) of its erythemal eiect. Thus, sunscreens cannot work without attenuating UVB. In recent years, especially in Europe, there has been a trend towards broad-spectrum sunscreens with good UVA protection. A standard method of de¢ning UVA protection has yet to be agreed and there is still controversy about the merits of UVA protection. The attenuation of UVB by sunscreen use is widely advocated to reduce skin cancer risk and the consumer has the right to know if such advice is evidence-based. In reality, it is largely based on mouse studies and molecular epidemiology which suggest that UVB is much more important than UVA, at least for non-melanoma skin cancer. There is only limited epidemiological evidence that sunscreen use inhibits actinic keratoses and squamous cell carcinoma but no evidence that sunscreens have any eiect in the prevention of basal cell carcinoma or malignant melanoma (IARC). The reasons that sunscreens may fail to inhibit skin cancer are too complex to be reviewed here, but may include their immunoprotective properties because UVR-induced immunosuppression is thought to play an important role in photocarcinogenesis. Thus, a sunscreen that aiorded protection from erythema without comparable protection from immunosuppression could enhance skin cancer risk. Concern about sunscreens’ability to inhibit UVR-induced immunosuppression has resulted in four human studies published in the Journal of Investigative Dermatology in 2003. These studies have assessed the capacity of sunscreens to inhibit UVR-induced suppression of either the induction arm or the elicitation arm of the contact hypersensitivity (CHS) response. In particular, all studies address the role of UVA in immunosuppression by asking the question: Are broad-spectrum sunscreens necessary to ensure comparable protection against erythema and immunosuppression? The principle behind the studies is to compare SPF with immune protection factor (IPF) with the same SSR source using an SSR dose-response approach. In theory, IPF1⁄4 SPF (i.e. IPF/ SPF1⁄41) if erythema and immunosuppression share a common chromophore(s) and both endpoints have dose-response curves with similar shapes that gives rise to similar action spectra. In the most recently published study in this issue, Baron et al (2003) have determined the IPF of two sunscreens with labelled SPFs of 15. One was primarily a UVB product with a UVA protection factor (UVA-PF) of 2 whilst the other was a broadspectrum sunscreen with a UVA-PF of 10. SPFs reported by the authors were 15.5 and 18.8 respectively, though lower values of 9.9 and 15.4 respectively were obtained on the study volunteers. IPF was determined by the ability of the sunscreens to inhibit SSRinduced suppression of the induction arm of the local CHS response using two readouts. Depending on the readout, the IPF of the UVB sunscreen was 11 or 15 (IPF/SPF1⁄4 0.7 to 1.5 depending on SPF and readout) whereas the IPF of the broad-spectrum product was 37 or 50 (IPF/SPF1⁄4 2.0 to 3.2 depending on SPF and readout). The data from the UVB sunscreen suggest that erythema and immunosupression share a common chromophore/action spectrum but, in contrast, the data from the broad-spectrum study suggest that UVA is much more immunosuppressive than it is erythemogenic. In other words, the action spectra for erythema and immunosuppression are very diierent. A possible explanation for these diierent conclusions is that higher dose UVA, as with the UVB sunscreen, enhances UVB-induced immunosuppression. Either way, the implication of this study is that there is a major, as yet unidenti¢ed, UVA chromophore(s) that plays a role in immunosuppression. However, in practice these data also suggest that UVB sunscreens give adequate immunoprotection (IPF/ SPF1⁄41), unless better immunoprotection than sunburn protection is considered bene¢cial. This is debatable because some immunosuppression may be desirable to prevent hypersensitivity reactions to photoantigens that may initiate photodermatoses such as polymorphic light eruption (van de Pas et al, in press). Baron et al (2003) used a study design that was essentially similar to those of Wolf et al (2003) and Kelly et al (2003). Wolf et al (2003) compared a UVB with a broad-spectrum sunscreen with SPFs of 5.2 and 6.2 respectively.The IPF was similar to the SPF of the UVB sunscreen (IPF/SPF1⁄4 0.9^1.1 depending on readout/ analysis) but higher than the SPF of the broad-spectrum product (IPF/SPF1⁄41.2^1.8). However, the IPF/SPFs of the two products were not signi¢cantly diierent. Kelly et al (2003) studied a single primarily UVB sunscreen and found the IPF to be less that 50% of its SPF (IPF/SPF1⁄4 0.4). It is very di⁄cult to reach a clear overall conclusion from these three studies. On the one hand, it could be argued that they support a mechanistic role for UVA in immunosuppression because the conclusions/speculations of their respective authors are qualitatively similar but it is clear that there are major quantitative diierences in the results that are rather dif¢cult to explain. On the other hand, only the study of Kelly et al (2003) suggests that broad-spectrum sunscreens are necessary to ensure that IPF/SPF1⁄41. It should be noted that these studies have used diierent skin type populations, readouts and/or methods of raw data processing and all studies used complex and diierent statistical analyses (each paper has statistician co-authorship). At present the authors are discussing a ‘‘meta-analysis’’ in which comparative analyses will be done with similar readouts/raw data processing and it will be interesting to see if the diierences in the results are due to any bias from data collection and analysis. This question has been approached to some extent by Wolf et al (2003) who reached similar conclusions with diierent readouts. It is noteworthy that Baron et al (2003) and Wolf et al (2003) have con¢rmed Kelly and colleagues (2003) observation that a single sub-erythemal SSR exposure is immunosuppressive. This implies that signi¢cant immunosuppression may occur even if a