We investigated the involvement of epidermal lipid peroxidation in the induction of ultraviolet radiation (UVR)-induced suppression of the skin immune system. The shaved dorsal skin of C3H/HeJ mice was irradiated with one of two subinflammatory solar-simulated UVR protocols 3 days per week for 4 weeks. Then half of 1 mg, 1, 2.5 or 5 mg alpha-tocopherol in a vehicle of acetone was topically applied to the shaved dorsal skin before UVR, A 5 mg dose of vitamin E gave complete protection against a UVR protocol that induced a 55% reduction in the contact hypersensitivity response to 2,4,6-trinitrochlorobenzene and a 23% reduction in epidermal Langerhans cell density. Lower doses were ineffective. alpha-Tocopherol was unable to protect against a higher UVR protocol. As 5 mg alpha-tocopherol did not prevent postirradiation inflammatory edema it is unlikely that the antioxidant acted as a sunscreen. However, 5 mg alpha-tocopherol inhibited UVR-induced epidermal lipid peroxidation, suggesting that this may be one mechanism by which alpha-tocopherol prevented UVR-induced local immunosuppression. Scavenging of UVR-generated lipid peroxides and reactive oxygen may have inhibited loss of cell membrane integrity preventing depletion of LC numbers, thus protecting from local immunosuppression.

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We investigated whether supplementation of a sunscreen containing the UVB absorber 2-ethyl-hexyl-methoxycinnamate (cinnamate) with oxygen radical inhibitors (ORI) would improve protection from sunburn, immunosuppression and carcinogenesis. Mice were exposed to solar-simulated UV radiation (ssUV) containing a mixture of UVB and UVA. In initial studies, the ORI 2,2'-dipyridyl and N(G)-monomethyl-L-arginine acetate (L-NMMA) were shown to prevent UVA-induced suppression of contact sensitivity (CS) in mice. Addition of these inhibitors to the sunscreen did not affect the sun protection factor (SPF), but lowered the level of edema when mice were exposed to ssUV. Combination of both inhibitors with the sunscreen, however, increased the SPF from 5 to 5.5. The immune protection factor (IPF) of the sunscreen was only 1.18, but addition of neither dipyridyl nor L-NMMA singly or in combination measurably improved immune protection. However, the ORI improved the ability of the sunscreen to prevent carcinogenesis. The results indicate that reactive oxygen or nitrogen species produced in response to UV radiation are important for erythema, immunosuppression and carcinogenesis, and addition of inhibitors improves the protective capacity of sunscreens.

Previous studies have indicated that sunscreens designed to protect from erythema do not adequately prevent immunosuppression. Mice were irradiated with suberythemal doses of solar-simulated ultraviolet radiation (ssUVR) to assess the immunoprotective ability of sunscreens. Whereas C3H/HeJ and BALB/c mice had similar sensitivities to ssUVR-induced inflammation, C3H/HeJ mice were more sensitive to ssUVR-induced immunosuppression. Octyl dimethyl-p-aminobenzoic acid did not protect from immunosuppression and, thus, had an immune protection factor (IPF) of 1. 2-Ethylhexyl-p-methoxycinnamate and microfine titanium dioxide provided limited protection, both having IPF values of 1.127. Immune protection by the sunscreens appeared to be dependent upon absorption of UVA as well as UVB, and was much less than predicted from the sun protection factor. Vitamin E, an inhibitor of lipid peroxidation, also protected the immune system, with an IPF of 1.2, indicating that oxidation of lipids is involved in UVR-induced immunosuppression, and that it should be possible to develop sunscreens which protect the immune system.

There is little evidence that cutaneous dendritic cells (DC), including epidermal Langerhans cells (LC), can induce immunity to UV radiation (UVR)‐induced skin tumours. Here, it is shown that cells within skin can induce protective antitumour immunity against a UVR‐induced fibrosarcoma. Transplantation of the skin overlying subcutaneous tumours onto naïve recipients could induce protective antitumour immunity, probably because the grafting stimulated the tumour Ag‐loaded DC to migrate to local lymph nodes. This suggests that cutaneous APC can present tumour Ag to induce protective antitumour immunity. Previously, it has been shown that immunization of mice with MHC class II+ epidermal cells (EC) pulsed with tumour extracts could induce delayed‐type hypersensitivity against tumour cells. Here, this same immunization protocol could induce protective immunity against a minimum tumorigenic dose of UVR‐induced fibrosarcoma cells, but not higher doses. Epidermal cells obtained from semiallogeneic donors and pulsed with tumour extract could also induce protective immunity. However, presentation of BSA Ag from the culture medium was found to contribute to this result using semiallogeneic EC. The results suggest that LC overlying skin tumours may be able to induce protective immunity to UVR‐induced tumours if stimulated to migrate from the skin.

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